Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.93550142
CCR 2 and CCR 5 interact primarily with the human CC family ligands CCL 2 ( formerly called monocyte chemoattractant protein ; MCP 1 ) , CCL 3 and CCL 4 ( macrophage inflammatory protein 1 alpha and 1 beta ; MIP 1 alpha / beta ) , and their main function is to recruit leukocytes from circulation into the tissues , thus playing an important role in human inflammatory disorders . 0.93550142^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.57519121
The signal transduction of MCPs on monocytes involves at least two G protein linked C C chemokine receptors : C C CKR 1 binds MCP 3 and C C CKR 2 binds MCP 1 and MCP 3 but not MCP 2 . 0.57519121^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.56793892
Here we report that the 35 amino terminal residues of CCR 2 , expressed as a membrane bound fusion protein , bound MCP 1 with an affinity similar to that of the intact , wild type receptor . 0.56793892^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.58512343
MCP 1 interacts with CCR2B receptor ( CCR2B ) , resulting in cell proliferation , haptotaxis , and healing of the monolayer . 0.58512343^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.61081502
We conclude that interaction of MCP 1 with CCR 2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP . . 0.61081502^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.63766141
However , the activation of CCR 2 with monocyte chemoattractant protein 1 not only stimulated the integrins preexisting on the cell surface , but also increased the number of CD11b molecules on the cell surface . 0.63766141^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Dexamethasone ( Dex ) up regulated mRNA expression of the monocyte chemotactic protein ( MCP 1 , CCL 2 ) chemokine receptor CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The most active chemokines for resting Th ( IL 10 ) , in terms of calcium mobilization and in vitro migration , were in order of potency : CCL 2 ( monocyte chemoattractant protein 1 , CCR 2 ligand ) , CCL 4 ( macrophage inflammatory protein 1beta , CCR 5 ligand ) , CCL 3 ( macrophage inflammatory protein 1alpha , CCR1 / 5 ligand ) , CCL 17 ( thymus and activation regulated chemokine , CCR 4 ligand ) , CCL 1 ( 1 309 , CCR 8 ligand ) , CXCL 12 ( stromal derived factor 1 , CXCR 4 ) , and CCL 11 ( eotaxin , CCR 3 ligand ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Blocking Gi protein coupled receptor signaling by pertussis toxin as well as deficiencies in G alpha 12 , chemokine receptor 2 ( CCR 2 ) , CCR 5 , chemokine ligand 2 ( CCL 2 , also known as monocyte chemoattractant protein 1 , or MCP 1 ) , CCL 3 ( macrophage inflammatory protein 1 alpha , or MIP 1 alpha ) and CCL 5 ( RANTES ) have all been found to have effects on the magnitude and cytokine polarity of the T cell response . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Moreover , activation of ERK1 / 2 was inhibited by pertussis toxin , a G ( 1 ) coupled protein inhibitor , and RS 504393 , CCR 2 antagonist , suggesting that ERK1 / 2 was activated by CCL 2 via CCR 2 and G ( 1 ) coupled protein . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 and its major ligand , chemokine ligand 2 ( CCL 2 ) / monocyte chemotactic protein 1 , have been found to influence T1 / T2 immune response polarization . ^^^ Our objective was to directly compare the roles of CCR 2 and CCL 2 in T1 / T2 immune response polarization using a model of pulmonary Cryptococcus neoformans infection . ^^^ Either deletion of CCR 2 or treatment of wild type mice with CCL 2 neutralizing Ab produced significant and comparable reductions in macrophage and T cell recruitment into the lungs following infection . ^^^ Both CCL 2 neutralization and CCR 2 deficiency resulted in significantly diminished IFN gamma production , and increased IL 4 and IL 5 production by lung leukocytes ( T 1 to T 2 switch ) , but only CCR 2 deficiency promoted pulmonary eotaxin production and eosinophilia . ^^^ In the lung associated lymph nodes ( LALN ) , CCL 2 neutralized mice developed Ag specific IFN gamma producing cells , while CCR 2 knockout mice did not . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The role of MCP 1 ( CCL 2 ) and CCR 2 in multiple sclerosis and experimental autoimmune encephalomyelitis ( EAE ) . ^^^ Evidence from descriptive , transgenic , knockout and neutralizing studies of experimental autoimmune encephalomyelitis ( EAE ) points towards a nonredundant role of CCL 2 and CCR 2 in the recruitment of inflammatory infiltrate into the CNS . ^^^ Hence , CCL 2 and CCR 2 may be targets for specific and effective treatment in MS . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The chemokine like , secreted protein product of the U 83 gene from human herpesvirus 6 , here named vCCL 4 , was chemically synthesized to be characterized in a complete library of the 18 known human chemokine receptors expressed individually in stably transfected cell lines . vCCL 4 was found to cause calcium mobilization as efficiently as the endogenous chemokine ligand CCL 2 through the CCR 2 receptor , whereas the virally encoded chemokine did not affect any of the other 17 human chemokine receptors tested . ^^^ Mutual cross desensitization between CCL 2 and vCCL 4 was demonstrated in the CCR 2 transfected cells . ^^^ The affinity of vCCL 4 for the CCR 2 receptor was 79 nm as determined in competition binding against radioactively labeled CCL 2 . ^^^ In the murine pre B lymphocyte cell line L1 . 2 stably transfected with the CCR 2 receptor , vCCL 4 acted as a relatively low potency but highly efficacious chemoattractant being equally or more efficacious in causing cell migration than CCL 2 and CCL 7 and considerably more efficacious than CCL 8 and CCL 13 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We investigated the role of monocyte chemotactic protein 1 ( CCL 2 , JE ) and the chemokine receptor CCR 2 in regulating alveolar leukocyte traffic . ^^^ Groups of wild type ( WT ) mice , CCR 2 deficient mice , lethally irradiated CCR 2 deficient and WT mice that were reciprocally bone marrow transplanted ( chimeric CCR 2 deficient and WT , respectively ) , chimeric CCR 2 deficient mice with an enriched CCR 2 ( + ) alveolar macrophage population , and CCR 2 deficient mice transfused with CCR 2 ( + ) mononuclear cells were treated with intratracheal CCL 2 and / or Escherichia coli endotoxin . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The CC chemokine ligand 2 ( CCL 2 ) ( JE , monocyte chemotactic protein 1 [ MCP 1 ] ) and its CC chemokine receptor 2 ( CCR 2 ) are critical regulators of monocyte / macrophage trafficking . ^^^ In this study , we investigated the role of the CCL 2 receptor CCR 2 in alveolar leukocyte traffic . ^^^ In CCR 2 knockout mice or wild type mice treated with the anti CCR 2 blocking monoclonal antibody MC 21 , monocyte accumulation in response to alveolar CCL 2 or CCL 2 plus endotoxin was inhibited by more than 90 % . ^^^ Wild type mice treated with MC 21 to block CCR 2 function or with anti Gr 1 to deplete neutrophils did not exhibit the vascular leakage that typically accompanies inflammation triggered by CCL 2 and LPS in wild type mice . ^^^ These findings confirm a central role for CCR 2 in the process of alveolar monocyte recruitment in response to CCL 2 alone and combined CCL 2 plus LPS and reveal a previously unobserved interdependence between monocyte and neutrophil trafficking that has important implications for the concomitant increase in vascular permeability . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
A direct effect of CCL 2 on tumor cells is to be excluded , either because primary tumors as well as cell lines have no detectable CCL 2 receptor ( CCR 2 ) and because addition of CCL 2 on tumor cells in vitro did not modify cell cycle progression or apoptosis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We found that murine islets produce monocyte chemoattractant protein 1 ( MCP 1 ; CCL 2 ) in vitro and that islet allograft rejection was associated with intragraft expression of MCP 1 and its receptor , CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We generated CCR 2 01 , a CCR 2 receptor specific monoclonal antibody that neither competes with the chemokine CCL 2 for binding nor triggers signaling , but nonetheless blocks replication of monotropic ( R 5 ) and T tropic ( X 4 ) HIV 1 strains . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In contrast to CD 16 monocytes , CD16+ monocytes expressed high CX3CR1 and CXCR 4 but low CCR 2 and CD62L levels and underwent efficient transendothelial migration in response to fractalkine ( FKN ; FKN / CX3CL1 ) and stromal derived factor 1 alpha ( CXCL 12 ) but not monocyte chemoattractant protein 1 ( CCL 2 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Mounting evidence suggests that CCL 2 ( MCP 1 ) and its hematopoietic cell receptor CC chemokine receptor 2 ( CCR 2 ) are involved in inflammatory disorders of the lung . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To address the role CCL 2 plays in oral tolerance , we used both CCL 2 ( / ) and CCR 2 ( / ) mice . ^^^ Cells from the spleen , mesenteric lymph nodes , and peripheral lymph nodes of CCL 2 ( / ) and CCR 2 ( / ) mice fed high doses of OVA showed robust proliferative responses compared with cells from Ag fed wild type mice . ^^^ CCL 2 ( / ) and CCR 2 ( / ) mice also produced high amounts of Th 1 cytokines such as IL 2 and IFN gamma and very low amounts of IL 4 and IL 10 . ^^^ The ability of APCs from the gut of CCL 2 ( / ) and CCR 2 ( / ) OVA fed mice to stimulate an indicator T cell line was evaluated . ^^^ These data indicate that CCL 2 and signaling through its receptor CCR 2 is critical for the induction of oral tolerance by regulating Ag presentation leading to a disruption in the balance of inflammatory and regulatory cytokines . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Examined were CCR 2 deficient mice to clarify the contribution of macrophages via monocyte chemoattractant protein 1 ( MCP 1 or CCL 2 ) / CCR2 signaling to the pathogenesis of renal ischemia reperfusion injury . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Post BMT lung injury occurs independently of the expression of CCL 2 or its receptor , CCR 2 , on host cells . ^^^ The major receptor for CCL 2 is CCR 2 present on monocytes ; this interaction can play a crucial role in monocyte recruitment in inflammation . ^^^ To determine whether blockade of the CCL2 / CCR2 pathway could hinder host monocyte influx , lethally conditioned wild type ( WT ) , CCL 2 ( / ) , or CCR 2 ( / ) mice were transplanted with allogeneic marrow and spleen cells . ^^^ Therefore , IPS can occur independently of host expression of CCL 2 or CCR 2 , and compensatory mechanisms exist for regulating APC recruitment into the lung during the early post BMT period . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
An animal model of age related macular degeneration in senescent Ccl 2 or Ccr 2 deficient mice . ^^^ Here we report that mice deficient either in monocyte chemoattractant protein 1 ( Ccl 2 ; also known as MCP 1 ) or its cognate C C chemokine receptor 2 ( Ccr 2 ) develop cardinal features of AMD , including accumulation of lipofuscin in and drusen beneath the retinal pigmented epithelium ( RPE ) , photoreceptor atrophy and choroidal neovascularization ( CNV ) . ^^^ Wild type choroidal macrophages degrade C 5 and IgG in eye sections of Ccl 2 ( / ) or Ccr 2 ( / ) mice . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
As a functional correlate , chemotaxis assays using the CCR 2 ligand , CCL 2 ( MCP 1 ) , were performed . ^^^ The increase in CCR 2 ( + ) LPLs in SBCD was confirmed by both immunohistochemistry ( p = 0 . 0002 ) and enhanced chemotactic responses to CCL 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 1 ( MCP 1 or CCL 2 ) and its receptor , CCR 2 , have been shown to play important roles in the development of Th 2 inflammation . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Induced macrophage migration in vivo is driven by the binding of monocyte chemoattractant protein 1 ( MCP 1 , or CCL 2 in the new nomenclature ) to the CCR 2 chemokine receptor on macrophages . ^^^ To determine whether the CCL 2 CCR2 signaling pathway is involved in the accumulation of macrophages in growing collateral vessels , we used mice that are deficient in CCR 2 in a model of experimental arterial occlusion and collateral vessel growth . ^^^ In an in vitro CCL 2 driven chemotaxis assay , mononuclear cells isolated from wild type BALB / c mice exhibited CCL 2 concentration dependent migration , whereas this migration was abolished in cells from CCR 2 ( / ) mice on a BALB / c genetic background . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCL 2 , released by glial cells , activates the chemokine receptor CCR 2 , causing the infiltration of blood monocytes in tissues affected by MS . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
OBJECTIVES : To investigate the production of dynamic alpha and beta chemokines represented by interleukin 8 ( IL 8 ) as alpha chemokine and CCL 2 ( monocyte chemoattractant protein 1 , CCR 2 ligand ) , CCL 4 ( macrophage inflammatory protein 1beta , CCR 5 ligand ) , CCL 3 ( macrophage inflammatory protein 1alpha , CCR1 / 5 ligand ) , ( CCL 5 , regulated upon activation , normal T cell expressed and secreted ( RANTES , CCR 5 ligand ) as beta chemokines by the human intestinal cell line INT 407 stimulated with factors produced by living Campylobacter jejuni ( C . jejuni ) and those present within sonicated and filtrated bacteria . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 , the receptor for CCL 2 , was more frequently expressed by iNKT compared with natural killer and T cells from blood ( P < 0 . 001 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
ERK is also activated by CCR 2 agonists , e . g . , monocyte chemoattractant protein 1 ( CCL 2 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
This was associated with reduced renal expression of CC chemokines CCL 2 , CCL 3 , CCL 4 , and CCL 5 and the chemokine receptors CCR 1 , CCR 2 , and CCR 5 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Tat treatment of microglia induced polarization of CCR 2 , the receptor for CCL 2 , to the leading edge of processes , further suggesting a CCL 2 dependent mechanism of tat induced microglia migration . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 positive monocytes recruited to inflamed lungs downregulate local CCL 2 chemokine levels . ^^^ The CC chemokine ligand 2 ( CCL 2 ) and its receptor CCR 2 are essential for monocyte trafficking under inflammatory conditions . ^^^ To determine the potential role of CCR 2 expressing monocytes in regulating alveolar CCL 2 levels , we compared leukocyte recruitment kinetics and alveolar CCL 2 levels in wild type and CCR 2 deficient mice in response to intratracheal LPS challenge . ^^^ In contrast , LPS treated CCR 2 deficient mice lacked alveolar monocyte accumulation , which was accompanied by relatively high CCL 2 levels in BALF . ^^^ Similarly , wild type mice that were treated systemically with the blocking anti CCR 2 antibody MC 21 completely lacked LPS induced alveolar monocyte trafficking that was associated with high CCL 2 levels in BALF . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The results showed that peritoneal production of the CCR 2 ligands CCL 2 and CCL 12 in septic mice was largely independent of the common Toll like receptor signaling adaptor MyD 88 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Differential roles of CCL 2 and CCR 2 in host defense to coronavirus infection . ^^^ Intracerebral infection of CCL 2 ( / ) mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR 2 ( / ) mice and CCL 2 ( / ) mice cleared replicating virus from the brain . ^^^ In contrast , CCR 2 ( / ) mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen specific T cells as compared to both CCL 2 ( / ) and wild type mice . ^^^ A similar reduction in macrophage infiltration into the CNS was observed in both CCL 2 ( / ) and CCR 2 ( / ) mice when compared to wild type mice , indicating that both CCL 2 and CC chemokine receptor 2 ( CCR 2 ) contribute to macrophage migration and accumulation within the CNS following MHV infection . ^^^ Together , these data demonstrate that CCR 2 , but not CCL 2 , is important in host defense following viral infection of the CNS , and CCR 2 ligand ( s ) , other than CCL 2 , participates in generating a protective response . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 1 ( also known as CC chemokine ligand 2 [ CCL 2 ] ) and its receptor CC chemokine receptor 2 ( CCR 2 ) play a central role in the inflammatory response and neointimal formation after vascular injury . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CC chemokine ligand 2 ( CCL 2 ) / monocyte chemotactic protein 1 , a member of the CC chemokine family , is a chemoattractant for monocytes and T cells through interaction with its receptor CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To do this , they have characterised haplotypes comprising alleles at 11 biallelic loci in four chemokine receptor genes ( CCR 3 , CCR 2 , CCR 5 and CCRL 2 ) , which span 150 kb on chromosome 3p21 , and haplotyes of nine biallelic loci in six chemokine genes [ MCP 1 ( CCL 2 ) , Eotaxin ( CCL 11 ) , RANTES ( CCL 5 ) , MPIF 1 ( CCL 23 ) , PARC ( CCL 18 ) and MIP 1alpha ( CCL 3 ) ] on chromosome 17q11 12 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Transplantation of islets with high levels of CCL 2 into syngeneic recipients led to a significantly greater influx of CCR 2 ( + ) cells and higher expression of monocyte / macrophage associated inflammatory cytokines compared with low CCL 2 donor islets . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The chemokine MCP 1 ( or CCL 2 ) plays a distinctive role in the recruitment of macrophages by predominantly stimulating the CCR 2 chemokine receptor . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Isolated lung fibrocytes expressed CCR 2 and migrated to CCL 2 , and CCL 2 stimulated collagen secretion by lung fibrocytes . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Expression of the chemokine receptors CCR 2 and CCR 5 by DC and their responsiveness to the respective ligands , CCL 2 and CCL 3 , were downregulated , while the level of CCR 7 and the DC response to its ligand CCL 21 were enhanced . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We report that aged ( > 6 months ) transgenic ( tg ) mice expressing CCL 2 under the control of the human glial fibrillary acidic protein promoter ( huGFAP CCL2hi tg+ mice ) manifested encephalopathy with mild perivascular leukocyte infiltration , impaired blood brain barrier function , and increased CD 45 immunoreactive microglia , which had morphologic features of activation . huGFAP CCL2hi tg+ mice lacking CC chemokine receptor 2 ( CCR 2 ) were normal , showing that chemokine action via CCR 2 was required . ^^^ Treatment with mutant CCL 2 peptides , a receptor antagonist and an obligate monomer , also suppressed morphological transformation in this assay , indicating a critical role for CCL 2 in microglial activation and suggesting that chronic CCL 2 exposure desensitized CCR 2 on microglia , which in the CNS of huGFAP CCL2hi tg+ mice , did not up regulate cell surface expression of major histocompatibility complex class 2 , CD11b , CD11c , or CD 40 , in contrast to recruited perivascular macrophages that expressed enhanced levels of these markers . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL 2 . ^^^ To test this hypothesis , we investigated the contribution of CCR 2 , the major cognate receptor for the chemokine CCL 2 ( formerly known as MCP 1 ) , to CCL 2 stimulated transendothelial migration of macrophages ( m ) across cultured brain microvascular endothelial cells ( BMEC ) . ^^^ Specifically , we prepared both BMEC and m from wild type ( WT ) mice and mice deficient in CCR 2 ; i . e . , CCR 2 ( / ) , and compared the ability of WT and CCR 2 ( / ) BMEC to support CCL 2 stimulated transendothelial migration of WT and CCR 2 ( / ) m . ^^^ In response to CCL 2 , WT m , but not CCR 2 ( / ) m , were stimulated to migrate across WT BMEC , consistent with the recognized obligatory role for CCR 2 in mediating CCL 2 stimulated responses . ^^^ Remarkably , however , neither WT nor CCR 2 ( / ) m were stimulated by CCL 2 to migrate across CCR 2 ( / ) BMEC . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The studies focused on the rat cerebellar Purkinje neuron , an identified CNS neuronal type reported to express both CCL 2 and its receptor , CCR 2 . ^^^ Immunohistochemical studies of Purkinje neurons in situ confirmed that they express CCR 2 and CCL 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Ligation of the chemokine receptor CCR 2 on monocytes and macrophages with its ligand CCL 2 results in activation of the cascade consisting of phosphatidylinositol 3 OH kinase ( PI ( 3 ) K ) , the small G protein Rac and lamellipodium protrusion . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Recruitment of this cell population and viral dissemination via the bloodstream to salivary glands proceeds normally in mice that lack CCR 2 and MCP 1 ( CCL 2 ) , suggesting that recruitment of macrophages is not a requisite component of pathogenesis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Hence , we investigated the effects of the lack of the major CCL 2 receptor , CCR 2 , on liver tumor formation induced by intraportal injection of the murine colon adenocarcinoma cell line , colon 26 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To test the hypothesis that chemokines exhibit previously undiscovered pleiotropic effects important for the behavioral actions of ethanol , we studied mutant mice with deletion of the Ccr 2 , Ccr 5 , Ccl 2 or Ccl 3 genes . ^^^ Deletion of Ccr 2 , Ccl 2 ( females ) or Ccl 3 in mice resulted in lower preference for alcohol and consumption of lower amounts of alcohol in a two bottle choice test as compared with wild type mice . ^^^ Ethanol treatment ( 2 . 5 g / kg , i . p . ) induced stronger conditioned taste aversion in Ccr 2 , Ccl 2 or Ccl 3 null mutant mice than in controls . ^^^ Ccr 2 and Ccr 5 null mutant mice did not differ from wild type mice in ethanol induced loss of righting reflex ( LORR ) , but mice lacking Ccl 2 or Ccl 3 showed longer LORR than wild type mice . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
At baseline , primed macrophages expressed a small subset of IFN gamma inducible genes , including CCR 2 , and exhibited increased migration in response to CCL 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Although adipose tissue expression and circulating concentrations of CCL 2 ( also known as MCP 1 ) , a high affinity ligand for CCR 2 , are elevated in obesity , the role of CCR 2 in metabolic disorders , including insulin resistance , hepatic steatosis , and inflammation associated with obesity , has not been studied . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The increased capacity of HIV infected leukocytes to transmigrate in response to CCL 2 correlated with their increased expression of CCR 2 , the chemokine receptor for CCL 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Here , we explored the effects of the glucocorticoid , corticosterone ( CORT ) , on the expression of CCL 2 and its receptors , CCR 2 and CCR 5 , in the hippocampal formation using intact , adrenalectomized ( ADX ) and trimethyltin ( TMT ) treated rats . ^^^ ADX , however , markedly increased the expression of CCL 2 and CCR 2 mRNAs in the hippocampus , while CORT replacement reversed the effects of ADX on CCL 2 gene expression . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Associations of polymorphisms in CCL 5 ( G 403A ) and its receptor CCR 5 ( Delta 32 ) , CCL 2 ( A 2578G ) and CCR 2 ( V64I ) , and CX3CR1 V249I and T280M with coal worker ' s pneumoconiosis ( CWP ) were investigated in 209 miners examined in 1990 , 1994 and 1999 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Although fibrocytes express an array of chemokine receptors , we observed an up regulation of CCR 2 expression following fibrocytes differentiation into adipocytes , which was associated with increased chemotactic response to CCL 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The latter coincided with increased secretion of CCL 2 by both astrocytes and brain endothelial cells and increased levels of the CCL 2 receptor , CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Modulating CCR 2 and CCL 2 at the blood brain barrier : relevance for multiple sclerosis pathogenesis . ^^^ CCR 2 is the major receptor for CCL 2 , a potent monocyte and T cell chemoattractant . ^^^ CCR 2 and CCL 2 have been consistently associated with a pathogenic role in experimental autoimmune encephalomyelitis , using knockout and transgenic mice , neutralizing antibodies , peptide antagonists and DNA vaccination . ^^^ However , the significance of CCL 2 and CCR 2 in multiple sclerosis is enigmatic , because CCL 2 levels are consistently decreased in the CSF of patients with this disease and other chronic neuroinflammatory conditions , despite abundant expression within lesional multiple sclerosis tissues . ^^^ This study used an in vitro BBB model to test the hypothesis that CCL 2 is removed from the extracellular fluid by CCR 2 positive migrating cells as they cross the BBB , resulting in decreased CSF CCL 2 levels . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In these cultures , specific inhibition of CCL 2 or CCR 2 attenuated the overexpression of alpha SMA , but not CTGF or plasminogen activator inhibitor 1 . ^^^ CCR 2 expression on SSc fibroblasts appears to regulate the expression of CCL 2 and alpha SMA . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 3 has been reported to induce [ Ca2+ ] 1 changes in cells transfected with the monocyte selective MCP 1 receptor 2B ( CC CKR2B ) and competes for 125I MCP 1 binding on CC CKR2B , suggesting that it may mediate monocyte responses to MCP 3 . ^^^ In contrast , binding to CC CKR2B was competed only by MCP 3 and MCP 1 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Using a set of overlapping lambda clones , the genomic organisation of the locus was investigated , demonstrating that the ChemR 13 gene is physically linked , and in the same orientation , as the CC CKR 2 gene that encodes a receptor for the monocyte chemoattractant protein 1 ( MCP 1 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Several receptors for MCP 1 and MCP 3 have been cloned from human monocytic cell lines , and one of these receptors , CCR2B , binds both MCP l and MCP 3 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In an effort to map the closely linked CC chemokine receptor genes , we identified a novel chemokine receptor encoded 18 kilobase pairs downstream of the monocyte chemoattractant protein 1 ( MCP 1 ) receptor ( CCR 2 ) gene on human chromosome 3p21 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
There are three ligands for CCR 2 in the mouse : CCL 2 , CCL 7 , and CCL 12 . ^^^ We now demonstrate that while CCR 2 / mice are protected from FITC induced fibrosis , CCL 2 / mice are not . ^^^ CCL 2 / mice are able to recruit fibrocytes to FITC injured airspaces , unlike CCR 2 / mice . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The CC chemokine ligand 2 ( CCL 2 ) and CC chemokine receptor 2 ( CCR 2 ) are expressed in the heart after infection with Trypanosoma cruzi , suggesting that they play an important role in host defense . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Functionally , it blocked MCP 1 ( CCL 2 ) induced calcium mobilization ( IC50=50 nM ) and chemotaxis mediated through the CCR 2 receptor ( 9 . 6 nM ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In this report , we characterized the heterodimerization of the CCR 2 ligands MCP 1 ( CCL 2 ) , MCP 2 ( CCL 8 ) , MCP 3 ( CCL 7 ) , MCP 4 ( CCL 13 ) , and eotaxin ( CCL 11 ) , as well as the effects of GAG binding , using electrospray ionization Fourier transform ion cyclotron resonance ( ESI FTICR ) mass spectrometry . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We found that infection of alveolar epithelial cells with the mouse adapted influenza A virus strain PR / 8 strongly induced the release of monocyte chemoattractants CCL 2 and CCL 5 followed by a strong monocyte transepithelial migration , and this monocytic response was strictly dependent on monocyte CCR 2 but not CCR 5 chemokine receptor expression . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Two human beta chemokine receptors have been cloned and characterized : the MIP 1 alpha / RANTES receptor or C C chemokine receptor 1 ( CCR 1 ) and the MCP 1 receptor or C C chemokine receptor 2 ( CCR 2 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Expression of the RANTES / MIP 1 alpha receptor ( CC CKR 1 ) and the MCP 1 receptor ( CC CKR 2 ) was highly correlated with migration toward RANTES , MCP 1 , and other CC chemokines , and was strictly dependent on the presence of IL 2 in the culture medium . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In this study , we show that the type B MCP 1R ( MCP 1RB / CCR2B ) is rapidly phosphorylated and internalized in response to nanomolar concentrations of MCP 1 . ^^^ Co expression of CCR2B in Xenopus oocytes with beta adrenergic receptor kinase 2 ( beta ark 2 ) , but not beta ark 1 or rhodopsin kinase , specifically blocked receptor activation by MCP 1 . ^^^ These studies demonstrate that phosphorylation of Ser and Thr residues in the carboxyl tail of CCR2B mediates receptor desensitization and internalization and may serve to limit the chemotactic response of leukocytes to MCP 1 and related chemokines . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Equilibrium binding studies revealed that those CCR2A receptors that successfully trafficked to the cell surface bound MCP 1 with high affinity ( Kd = 310 pM ) , similar to CCR2B . ^^^ These data indicate that the alternatively spliced form of the human MCP 1 receptor ( CCR2A ) binds MCP 1 with high affinity and is a functional receptor and that expression at the cell surface is controlled by amino acid sequences located in the terminal carboxyl tail . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 2 can exert its effects through the MCP 1 receptor ( CC CKR2B ) . ^^^ We studied the activities of the monocyte chemoattractant proteins MCP 1 , MCP 2 and MCP 3 on human embryonic kidney 293 EBNA cells transfected with the MCP 1 receptor ( CC CKR2B ) . ^^^ In conclusion , our data indicate that MCP 2 can exert its effects through the MCP 1 receptor , CC CKR2B . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Conversely , a chimeric receptor with the N terminus of CCR 2 replacing that of CCR 5 responded to macrophage inflammatory protein 1beta and MCP 1 but did not efficiently support viral entry . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
It was therefore of interest to define the expression in resting and activated NK cells of the MCP 1 receptor ( CCR 2 ) for which two cDNAs ( A and B ) have been described . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
As shown by calcium flux assays , MCP 4 activated the cloned G protein coupled receptor CCR 2 , which also recognizes MCP 1 and MCP 3 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 induced rapid and transient activation of MAPK in human monocytes and in Chinese hamster ovary cells expressing CCR2B . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 2 ( MCP 2 ) uses CCR 1 and CCR2B as its functional receptors . ^^^ In experiments using cells transfected with C C chemokine receptors , 125I MCP 2 bound to human embryonic kidney 293 cells transfected with CCR 1 or CCR2B , known to also bind MIP 1alpha / RANTES and MCP 1 , respectively , but both shared by MCP 3 . ^^^ Both CCR 1 and CCR2B transfected 293 cells showed significant migration in response to MCP 2 , in addition to responding to other specific chemokines . ^^^ These results clearly demonstrate that MCP 2 , unlike MCP 1 , uses both CCR 1 as well as CCR2B as its functional receptors , and this accounts for the unique activities of MCP 2 . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
LPS caused a rapid and drastic reduction of CCR 2 mRNA levels , which binds MCP 1 and 3 . ^^^ As expected , LPS induced inhibition of CCR 2 mRNA expression was associated with a reduction of both MCP 1 binding and chemotactic responsiveness . ^^^ In contrast , IL 2 augmented CCR 2 expression and MCP 1 itself had no effect . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 and CCR 2 in HIV infection : regulation of agonist and receptor expression . ^^^ Monocyte chemotactic protein 1 ( MCP 1 ) interacts with the chemokine receptor CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We studied the effect of the chemokine monocyte chemoattractant protein 1 ( MCP 1 ) and of a panel of MCP 1 receptor ( CCR 2 ) specific monoclonal antibodies ( mAb ) on the suppression of HIV 1 replication in peripheral blood mononuclear cells . ^^^ Furthermore , mAb specific for the MCP 1R CCR 2 which recognize the third extracellular CCR 2 domain inhibit all MCP 1 activity and also block MCP 1 suppressive activity . ^^^ Finally , a set of mAb specific for the CCR 2 amino terminal domain , one of which mimics MCP 1 activity , has a potent suppressive effect on HIV 1 replication in M and T tropic HIV 1 viral isolates . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In contrast , the antibody did not affect the responses induced by MCP 1 , MCP 3 , and macrophage inflammatory protein 1alpha , which may depend on CCR 1 and CCR 2 , two additional receptors detected by Northern blotting with basophil RNA . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 5 is most closely related to CCR2b , another chemokine receptor that responds to monocyte chemoattractant protein ( MCP ) 1 , MCP 2 , MCP 3 , and MCP 4 . ^^^ Conversely , the NH 2 terminal domain of CCR2b is responsible for the high affinity binding of MCP 1 , but is not sufficient to confer activation of the intracellular cascades . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Desensitization studies indicated that MCP 1 and MCP 3 function through CCR 2 on these cells . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 3 ( MCP 3 ) is a C C chemokine which interacts with the CCR 1 , CCR 2 ( MCP 1 ) and CCR 3 receptors and has a distinct spectrum of action . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
However , mRNA encoding the macrophage MCP 1 receptors , CCR2A and B , is not present in SMC , indicating that they possess a distinct MCP 1 receptor . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Removal of glycosaminoglycans from CHO cells expressing chemokine receptors CXCR 1 , CCR 1 , or CCR 2 resulted in 40 70 % decreases in the binding of RANTES , MCP 1 , IL 8 , and MIP 1alpha . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
One C C chemokine receptor , CCR 2 , has been identified that mediates in vitro responses to MCP 1 and its close structural homologues . ^^^ These results suggest that CCR 2 has a nonredundant role as a major mediator of macrophage recruitment and host defense against bacterial pathogens and that MCP 1 and other CCR 2 ligands are effectors of those functions . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To determine the role of MCP 1 and related family members in vivo , we used homologous recombination in embryonic stem cells to generate mice with a targeted disruption of C C chemokine receptor 2 ( CCR 2 ) , the receptor for MCP 1 . ^^^ In in vitro chemotaxis assays , CCR 2 / leukocytes failed to migrate in response to MCP 1 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 1 ( MCP 1 ) induced LFA 1 dependent transendothelial migration of Jurkat and J beta 2 . 7 transfectants coexpressing the MCP 1 receptor CCR2B and wild type alpha L . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The binding and functional activity of the CC chemokines monocyte chemoattractant protein 1 ( MCP 1 ) , MCP 2 , and MCP 3 have been characterized using Chinese hamster ovary DXB 11 cells transfected with the chemokine receptor CCR2B . ^^^ These data demonstrate that MCP 2 , in addition to MCP 1 and MCP 3 , is a potent agonist of CCR2B and furthermore that MCP 2 activates either different or a subset of the signaling pathways activated by MCP 1 and MCP 3 . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 3 ( MCP 3 ) is a C C chemokine which interacts with the CCR 1 , CCR 2 ( MCP 1 ) and CCR 3 receptors and has a distinct spectrum of action . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Because other chemokines have similar target cell specificities and because CCR 2 , a cloned MCP 1 receptor , binds other ligands , it has been uncertain whether MCP 1 plays a unique role in recruiting mononuclear cells in vivo . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 2 is also a member of the CC chemokine subfamily and has the capacity to interact with at least two receptors including CCR 1 and CCR2B . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 1 ( MCP 1 ) is a member of the chemokine cytokine family , whose physiological function is mediated by binding to the CCR 2 and CCR 4 receptors , which are members of the G protein coupled receptor family . ^^^ In this report , we show that MCP 1 binding to the CCR 2 receptor in Mono Mac 1 cells promotes the rapid desensitization of MCP 1 induced calcium flux responses . ^^^ Calcium flux responses to MCP 1 in HEK 293 cells expressing the CCR2B receptor were also markedly reduced upon cotransfection with GRK 2 or the homologous kinase GRK 3 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Messenger RNA for the MIP 1alpha / RANTES receptor , CCR 1 , and the MCP 1 / MCP 3 receptor , CCR 2 , was expressed by unstimulated VSMCs grown under serum free culture conditions for 24 hours . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Thus , IFN gamma , an inducer of MCP 1 and MCP 3 in mononuclear phagocytes , selectively inhibits expression of the MCP receptor CCR 2 in monocytes . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Using the Mono Mac 1 monocytic cell line , we show that monocyte chemotactic protein 1 ( MCP 1 ) triggers activation of the Janus kinase 2 ( JAK 2 ) / STAT3 pathway and CCR 2 receptor tyrosine phosphorylation . ^^^ Within seconds of MCP 1 activation , JAK 2 phosphorylates CCR 2 at the Tyr 139 position and promotes JAK2 / STAT3 complex association to the receptor . ^^^ This MCP 1 initiated phosphorylation and association to JAK 2 is also observed in CCR2B transfected HEK 293 cells . ^^^ In contrast , when a CCR2B Tyr139Phe mutant is expressed in HEK 293 cells , it is not phosphorylated in tyrosine and triggers neither JAK2 / STAT3 activation nor Ca2+ mobilization in response to MCP 1 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The chemokines monocyte chemotactic protein ( MCP ) 3 , MCP 4 , and eotaxin acted like RANTES , whereas macrophage inflammatory protein ( MIP ) 1alpha , MIP 1beta , MCP 1 , and stromal cell derived factor 1 were inactive , suggesting a role for the eotaxin receptor , CCR 3 , and ruling out the involvement of CCR 1 , CCR 2 , CCR 5 , and CXCR 4 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The MCP 1 induced calcium mobilization mediated by CCR2b signaling was unaffected by the polymorphism , but MCP 1 signaling mediated by either CCR2b or CCR 2 V64I encoded receptors resulted in heterologous desensitization ( i . e . , limiting the signal response of other receptors ) of both CCR 5 and CXCR 4 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The eotaxin structure is compared with the chemokines regulated upon activation , normal T cell expressed and secreted ( RANTES ) and monocyte chemoattractant protein 1 ( MCP 1 ) ; eotaxin binds only CC chemokine receptor CCR 3 , whereas RANTES binds many receptors including CCR 3 , and MCP 1 binds a distinct receptor , CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To determine whether MCP 1 is causally related to the development of atherosclerosis , we generated mice that lack CCR 2 , the receptor for MCP 1 ( ref . 7 ) , and crossed them with apolipoprotein ( apo ) E null mice which develop severe atherosclerosis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The characterization of these mAbs includes the ability to recognize the CCR 2 receptor specifically , as well as the function based on their ability to promote Ca2+ influx or to block MCP 1 induced Ca2+ influx and chemotaxis . ^^^ One mAb ( MCP 1 R 02 ) that is directed to the NH 2 terminal domain of the CCR 2 receptor has MCP 1 agonist activity , and two that recognize the third extracellular domain ( MCP 1R04 and MCP 1 R 05 ) have MCP 1 antagonist activity . ^^^ Moreover , both MCP 1 and the agonist mAb trigger specific B cell migration via a PTX sensitive mechanism , indicating the presence of a functional CCR 2 receptor in these cells . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monomeric monocyte chemoattractant protein 1 ( MCP 1 ) binds and activates the MCP 1 receptor CCR2B . ^^^ To address the role of dimerization in the function of the monocyte chemoattractant protein 1 , MCP 1 , we mutated residues that comprise the core of the dimerization interface and characterized the ability of these mutants to dimerize and to bind and activate the MCP 1 receptor , CCR2b . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Cultures of isolated lung fibroblasts from L NAME treated mice expressed higher levels of C C chemokine receptor 2 ( CCR 2 ) and CCR 3 mRNA and contained less MCP 1 and eotaxin protein than a similar number of fibroblasts from D NAME treated mice . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The recruitment of monocytes to the intima requires the interaction of locally produced chemokines with specific cell surface receptors , including the receptor ( CCR 2 ) for monocyte chemoattractant protein 1 ( MCP 1 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In leukocytes , MCP 1 activates the pertussis toxin sensitive CCR 2 receptor . ^^^ However , transcripts for CCR 2 could not be shown in HSC , and pertussis toxin only modestly inhibited MCP 1 induced migration . ^^^ MCP 1 dependent signals in these cells are not transduced by CCR 2 and may be mediated by alternative chemokine receptors . ( HEPATOLOGY 1999 ; 29 : 140 148 . ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Human MCP 1 / murine JE , a myelosuppressive chemokine , specifically binds C C chemokine receptor 2 ( CCR 2 ) . ^^^ Transgenic mice containing a targeted disruption in CCR 2 that prevents expression of CCR 2 mRNA and protein and have MPC that are insensitive to inhibition by MCP 1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow ( BM ) and spleen MPC . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In contrast , MCP 1 and CCR 2 but not GRO alpha and CXCR 2 mediated spreading , shape change and subsequent transendothelial migration , which was evident in flow but rarely in stasis and may thus require the establishment of a diffusible MCP 1 gradient . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The CC chemokine monocyte chemoattractant protein 1 ( MCP 1 ) and its specific receptor CCR 2 are essential in monocytic infiltration and have been associated with several inflammatory diseases . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In contrast , staining for an activation epitope revealed a rapid and transient up regulation of LFA 1 activity by monocyte chemotactic protein 1 ( MCP 1 ) in monocytes and Jurkat CCR 2 chemokine receptor transfectants or by stromal derived factor 1alpha in Jurkat cells . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To determine whether the receptor for MCP 1 , CC chemokine receptor CCR 2 , plays a role in atherogenesis , CCR 2 deficient animals were crossed with mice lacking apo E , a well characterized model of atherosclerosis . ^^^ These studies directly demonstrate that the MCP 1 receptor , CCR 2 , plays an important role in atherogenesis . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
C C chemokine receptor 2 ( CCR 2 ) is considered the major G protein coupled receptor for MCP 1 / JE . ^^^ In granulomatous lungs , CCR 2 knockout increased mRNA for CCR 2 agonists , MCP 1 , MCP 3 , and MCP 5 , but reduced IL 4 and IFNgamma mRNA . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The accumulation of monocytes is mediated by the interaction of locally produced chemoattractant protein 1 ( MCP 1 ) with its receptor CCR 2 . ^^^ The physiological significance of altered CCR 2 expression was tested by chemotaxis assay , and our results demonstrated that treatment of THP 1 monocytes with LDL induced CCR 2 expression and substantially enhanced the chemotaxis elicited by MCP 1 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Loss of CCR 2 expression and functional response to monocyte chemotactic protein ( MCP 1 ) during the differentiation of human monocytes : role of secreted MCP 1 in the regulation of the chemotactic response . ^^^ The loss of CCR 2 mRNA expression in 7 day cultured macrophages was associated with a strong reduction in the receptor expression at the plasma membrane , as well as in the monocyte chemotactic protein ( MCP 1 ) binding , as compared with freshly isolated monocytes . ^^^ Differentiation of monocytes into macrophages also resulted in an increased secretion of MCP 1 that , at least in part , was responsible for the downmodulation of its receptor ( CCR 2 ) . ^^^ The loss of CCR 2 expression and the parallel increase of MCP 1 secretion triggered by differentiation may represent a feedback mechanism in the regulation of the chemotactic response of monocytes / macrophages . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
At the exposure times studied ( 30 90 min ) hypoxia does not affect expression of the MCP 1 receptor CCR2B and cells exposed to hypoxia still respond to MCP 1 with an elevation of intracellular calcium . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 1 ( MCP 1 ) and its receptor CCR 2 are important for monocyte extravasation and formation of atherosclerotic lesions . ^^^ Flow cytometric analysis revealed that monocytoid Mono Mac 6 cells that had transmigrated endothelium towards a MCP 1 gradient expressed higher levels of CCR 2 than the non migratory fraction , while input cells were intermediate , suggesting that high CCR 2 levels are essential for transendothelial chemotaxis . ^^^ Pretreatment of Mono Mac 6 cells or isolated human blood monocytes with the inflammatory cytokine tumor necrosis factor ( TNF ) alpha dose and time dependently reduced MCP 1 induced transendothelial chemotaxis , which was inhibited by the CCR 2 receptor antagonist 9 76 analog . ^^^ In conclusion , TNF alpha impairs MCP 1 induced transendothelial migration of monocytes by downregulating CCR 2 which appears critical for migration . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Airway hyperreactivity was mediated by MCP 1 through CCR 2 because allergen induced as well as direct MCP 1 instilled induced changes in airway hyperreactivity were significantly attenuated in CCR 2 / mice . ^^^ Thus , these data identify MCP 1 and CCR 2 as potentially important therapeutic targets for the treatment of hyperreactive airway disease . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Expression of CCR 2 by endothelial cells : implications for MCP 1 mediated wound injury repair and In vivo inflammatory activation of endothelium . ^^^ Reverse transcription polymerase chain reaction , RNase protection , Western blot , and flow cytometric analysis showed that human umbilical vein endothelial cells express mRNA and surface protein of the monocyte chemotactic protein 1 ( MCP 1 ) receptor CCR 2 , which was upregulated by inflammatory cytokines . ^^^ Increased secretion of MCP 1 or interleukin 8 , but not RANTES , on endothelial injury suggested a functional role of CCR 2 in wound repair as measured by ELISA . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Similarly , the CCR2b ligands MCP 1 and MCP 3 inhibit productive infection of PBMCs by both CCR 5 and CXCR 4 dependent strains of HIV 1 , suggesting that expression of the MCP 1 chemokine may affect HIV infection via signaling through the CCR 2 receptor and subsequent desensitization of the CCR 5 and / or CXCR 4 signaling pathway . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We find that MIF inhibition of chemotaxis does not occur at the level of the CC chemokine receptor for MCP 1 , CCR 2 , since MIF does not alter the binding of ( 125 ) 1 MCP 1 to monocytes . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Identification of residues in the monocyte chemotactic protein 1 that contact the MCP 1 receptor , CCR 2 . ^^^ To identify the regions of MCP 1 that contact its receptor , CCR 2 , we substituted all surface exposed residues with alanine . ^^^ It was previously shown that the N terminus of CCR 2 is critical for binding MCP 1 [ Monteclaro , F . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The physiological cellular responses to monocyte chemoattractant protein 1 ( MCP 1 ) , a potent chemotactic and activating factor for mononuclear leukocytes , are mediated by specific binding to CCR 2 . ^^^ Replacement of the first extracellular loop of CCR 2 with the corresponding region of CCR 1 decreased the MCP 1 binding affinity about 10 fold and prevented transmembrane signaling . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In this review , we will discuss our present knowledge about MCP 1 and its receptor CCR 2 and their role in atherogenesis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Changes in MCP 1 , C C chemokine receptor 2 ( CCR 2 ) , procollagen 1 and 3 , and TGF beta were examined in fibroblasts cultured from normal lung and from nonfibrotic ( i . e . , Th 1 type ) and fibrotic ( i . e . , Th 2 type ) pulmonary granulomas . ^^^ Taken together , these findings suggest that lung fibroblasts are altered in their expression of MCP 1 , TGF beta , CCR 2 , and procollagen following their participation in pulmonary inflammatory processes , and these changes may be important during fibrosis . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Binding of labeled MCP 1 was also inhibited by unlabeled MCP 3 , both of which are ligands for CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The CC chemokine , monocyte chemotactic protein , 1 ( MCP 1 ) functions as a major chemoattractant for T cells and monocytes by interacting with the seven transmembrane G protein coupled receptor CCR 2 . ^^^ To identify which residues of MCP 1 contribute to signaling though CCR 2 , we mutated all the surface exposed residues to alanine and other amino acids and made some selective large changes at the amino terminus . ^^^ Furthermore , it suggests that specific molecular features of MCP 1 induce different conformations in CCR 2 that are coupled to separate postreceptor pathways . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
During the development of nephrotoxic nephritis ( NTN ) in the mouse , we find that a variety of chemokines and chemokine receptors are induced : CCR 1 ( RANTES , MIP 1alpha ) , CCR 2 ( MCP 1 ) , CCR 5 ( RANTES , MIP 1alpha , MIP 1beta ) , CXCR 2 ( MIP 2 ) , and CXCR 3 ( IP 10 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 is a prominent receptor for monocyte chemoattractant protein 1 ( MCP 1 ) . ^^^ It has been suggested that CCR 2 and its ligand , MCP 1 , play a role in the pathogenesis of glomerulonephritis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 binds the chemokine receptor CCR 2 . ^^^ TAM isolated from ascitic or solid ovarian carcinoma displayed defective CCR 2 mRNA ( Northern blot and PCR ) and surface expression and did not migrate in response to MCP 1 . ^^^ CCR 2 gene expression and chemotactic response to MCP 1 were decreased to a lesser extent in blood monocytes from cancer patients . ^^^ CCR 2 mRNA levels and the chemotactic response to MCP 1 were drastically reduced in fresh monocytes cultured in the presence of tumor ascites from cancer patients . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We hypothesized that if MCP 1 regulates macrophage / microglial infiltration , then expression of the specific MCP 1 receptor , CCR 2 , will be induced in peritumoral tissue and / or within brain tumors . ^^^ RT PCR analysis showed high levels of both MCP 1 and CCR 2 mRNA and Western blot analysis demonstrated increased CCR 2 protein in tumor extracts . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The activation of the target cells by MCP 3 is via specific chemokine receptors CCR 2 and CCR 3 , of which CCR 2 is shared with MCP 1 . ^^^ MCP 1 and CCR 2 have been implicated in vascular diseases including atherosclerosis and restenosis , that are known to be involved in inflammation ( accumulation of T lymphocytes and monocytes ) and smooth muscle cell ( SMC ) activation ( proliferation , migration and matrix deposition ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattracant 1 ( MCP 1 ) stimulates leukocyte chemotaxis to inflammatory sites , such as rheumatoid arthritis , atherosclerosis , and asthma , by use of the MCP 1 receptor , CCR 2 , a member of the G protein coupled seven transmembrane receptor superfamily . ^^^ One of the more potent compounds blocks MCP 1 binding to CCR 2 with a K ( d ) of 60 nm , but it is unable to block binding to CXCR 1 , CCR 1 , or CCR 3 . ^^^ We showed that glutamate 291 ( Glu ( 291 ) ) of CCR 2 is a critical residue for high affinity binding and that this residue contributes little to MCP 1 binding to CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In addition , CXCR 1 , CXCR 2 and CCR2b , receptors for IL 8 and MCP 1 , respectively , were also found to be upregulated in TH 4 7 5 versus 85HG66 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Notably , CaR activation of monocytes bearing the receptor synergistically augmented the transmigration response of monocytes to the chemokine MCP 1 in association with increased cell surface expression of its cognate receptor , CCR 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 in pleural injury : CCR 2 mediates haptotaxis of pleural mesothelial cells . ^^^ We hypothesized that monocyte chemoattractant protein 1 ( MCP 1 ) induces proliferative and haptotactic responses in pleural mesothelial cells ( PMCs ) and that the MCP 1 binding receptor CCR 2 mediates the pleural repair process . ^^^ Blocking the CCR 2 with neutralizing antibodies decreased the haptotactic response of PMCs to MCP 1 . ^^^ These results suggest that the haptotactic migration of mesothelial cells in response to MCP 1 are mediated through CCR 2 , which may play a crucial role in reepithelialization of the denuded basement membrane at the site of pleural injury and may thus contribute to the regeneration of the mesothelium during the process of pleural repair . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In subjects with COPD , semi quantitative analysis revealed 1 . 5 fold higher levels of MCP 1 mRNA and IL 8 mRNA and protein in bronchiolar epithelium ( p < 0 . 01 ) and 1 . 4 fold higher levels of CCR 2 in macrophages ( p=0 . 014 ) than in subjects without COPD . ^^^ The bronchiolar epithelial MCP 1 mRNA expression correlated with both CCR 2 expression on macrophages and mast cells ( p < 0 . 05 ) and the numbers of intra epithelial macrophages and mast cells ( p < 0 . 04 ) . ^^^ These data suggest that MCP 1 and CCR 2 are involved in the recruitment of macrophages and mast cells into the airway epithelium in COPD . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The C C chemokine receptor , CCR 2 , has been identified as the primary receptor that mediates monocyte chemoattractant protein 1 ( MCP 1 ) responses in the mouse . ^^^ Significantly elevated levels of MCP 1 were detected in liver samples from CCR 2 ( + / + ) and CCR 2 ( / ) mice at 24 hours post APAP . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Localisation of mRNA for JE / MCP 1 and its receptor CCR 2 in atherosclerotic lesions of the ApoE knockout mouse . ^^^ In the present study , we have used in situ hybridisation to examine the gene expression of JE , the murine homologue of MCP 1 , and its receptor , CCR 2 , during the development of atherosclerotic lesions in the ApoE knockout mouse . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Multicolor flow cytometric analysis of whole peripheral blood revealed that , as opposed to CD14++ monocytes , the CD14+CD16+ subset lacked surface expression of monocyte chemotactic protein 1 ( MCP 1 ) receptor CCR 2 , however , it showed significantly higher surface expression of the macrophage inflammatory protein 1alpha ( MIP 1alpha ) / RANTES receptor CCR 5 . ^^^ Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14+CD16+ cells was dramatically reduced in the fraction migrating toward MCP 1 compared with the fraction that did not migrate or the input , showing that polarized CCR 2 expression was accompanied by a differential chemotactic responsiveness . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Infected CCR 5 ( / ) mice and CCR 2 ( / ) mice both exhibited increased expression of the gene for MCP 1 , the major ligand for CCR 2 ( / ) and a key regulator of induced macrophage migration . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Human endothelial cells express CCR 2 and respond to MCP 1 : direct role of MCP 1 in angiogenesis and tumor progression . ^^^ Moreover , the direct effect of MCP 1 on angiogenesis was consistent with the expression of CCR 2 , the receptor for MCP 1 , on endothelial cells . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Ligands for CCR 2 and CCR 3 include MCP 1 and MCP 3 which were co localised around vessels with the infiltrating leukocytes , but were also present in unaffected areas of cortex . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Ligands for CCR 2 and CCR 5 ( chemokines monocyte chemotactic protein 1 [ MCP 1 ] and RANTES ) are implicated in the pathogenesis of sarcoidosis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Recent studies have documented increased expression of MCP 1 in diverse acute and chronic experimental brain injury models ; in contrast , there is little information regarding expression of the MCP 1 receptor , CCR 2 , in the brain . ^^^ To determine if MCP 1 could be a regulator of this response , we evaluated the impact of excitotoxic injury on MCP 1 and CCR 2 expression in the neonatal rat brain . ^^^ We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA ( 10 nmol ) in 7 day old rats , to examine injury induced alterations in MCP 1 and CCR 2 expression . ^^^ RT PCR assays demonstrated rapid stimulation of both MCP 1 and CCR 2 mRNA expression . ^^^ These results demonstrate that in the neonatal brain , acute excitotoxic injury stimulates expression of both MCP 1 and its receptor , CCR 2 , and suggests that MCP 1 regulates the microglial / monocyte response to acute brain injury . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Consistent with this concept , expression of the MCP 1 receptor CCR 2 decreases with monocyte differentiation , as production of cytokines increases ( Fantuzzi et al . , 1999 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The present study investigates the course of Wallerian degeneration after transection of the sciatic nerve in mice deficient in two chemokine receptors : CCR 2 , the main receptor for MCP 1 , and CCR 5 , a marker for Th 1 T lymphocytes but also present on macrophages . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We extend these findings in this report to reveal that such sites exemplify characteristics of the recognized major receptors for MCP 1 and MIP 1alpha : CCR 2 , and CCR 1 and CCR 5 , respectively . ^^^ Specifically , labeled MCP 1 binding to isolated brain microvessels was inhibited by unlabeled MCP 1 and MCP 3 , the latter another CCR 2 ligand , but not by MIP 1alpha . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Five fold more MCP 1 was required to initiate chemotaxis of the CCR2A low transfectant , but the peak of chemotaxis was similar for the CCR2A and CCR2B transfectants expressing similar numbers of receptors . ^^^ MCP 1 induced chemotaxis was sensitive to pertussis toxin , implying that both CCR2A and CCR2B are G ( 1 ) alpha protein coupled . ^^^ In contrast , MCP 1 did not induce Ca ( 2+ ) flux in the CCR2A transfectant . ^^^ Since MCP 1 can stimulate chemotaxis of the CCR2A transfectant without inducing Ca ( 2+ ) mobilization , Ca ( 2+ ) flux may not be required for MCP 1 induced chemotaxis in the Jurkat transfectants . ^^^ Nanomolar concentrations of MCP 1 induced chemotaxis in the CCR2B transfectants that express high , intermediate , and low levels of MCP 1R . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemotactic protein 1 ( MCP 1 ) binding to its receptor , CCR2B , plays an important role in a variety of diseases involving infection , inflammation , and / or injury . ^^^ Human embryonic kidney 293 cells expressing Flag tagged CCR2B containing site directed mutations in this region , 21 26 , including a consensus tyrosine sulfation site were used to determine MCP 1 binding and its biological consequences . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Therefore , the expression of monocyte chemoattractant protein 1 ( MCP 1 ) , its receptor chemokine receptor 2B ( CCR2B ) , and CCR 5 in human cGN was studied . ^^^ MCP 1 and CCR2B mRNA expression was evaluated , by in situ hybridization , in serial sections of 23 renal biopsies from patients with cGN . ^^^ The number of glomerular macrophages was associated with the number of MCP 1 and CCR2B positive glomerular cells . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Blocking mAbs to CCR 2 and CCR 3 demonstrated that responses to higher concentrations ( > 10 nM ) of MCP 1 were mediated by CCR 3 rather than CCR 2 , whereas MCP 4 exhibited a biphasic response consistent with sequential activation of CCR 3 at lower concentrations and CCR 2 at 10 nM MCP 4 and above . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 ( / ) mice immunized with MOGp 35 55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES ( regulated on activation , normal T cell expressed and secreted ) , MCP 1 , and interferon ( IFN ) inducible protein 10 ( IP 10 ) as well the chemokine receptors CCR 1 , CCR 2 , and CCR 5 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 1 ( MCP 1 ) is an important chemokine for monocyte recruitment , and its receptor ( CCR 2 ) may mediate such in vivo response . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
While mRNAs encoding the IL 8 receptor , CXCR 2 , and the MCP 1 receptor , CCR 2 , were increased in U 937 cells cultured in 5 10 % Product R , we observed no change in binding of receptor specific antibodies . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
First , mRNA levels encoding the chemokines MIG , RANTES , lymphotactin , MIP 3alpha , TCA 3 , TARC , MIP 3beta , LIX , MCP 1 and MIP 1beta and the receptors CCR 4 , CCR 6 and CCR 2 were significantly increased in chronically inflamed colons of IL 10 / mice when compared with wildtype mice . ^^^ Interestingly , reversal of colitis in IL 10 / mice by anti IL 12 mAb was accompanied by the inhibition in the expression of LIX , lymphotactin , MCP 1 , MIG , MIP 3alpha , MIP 3beta , TCA 3 , CCR 2 and CCR 4 , whereas the increased mRNA levels of MIP 1beta , RANTES , TARC and CCR 6 were unaffected . ^^^
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This effect of irbesartan on MCP 1 occurred without an effect on CCR 2 , the receptor of MCP 1 . ^^^
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Because MCP 1 , acting through its receptor CCR 2 , is a potent mononuclear cell chemoattractant , we hypothesized that expression of this chemokine during an allogeneic response promotes persistent recruitment of leukocytes and , ultimately , rejection . ^^^ Translational studies in a murine model of BOS demonstrated increased MCP 1 expression paralleling mononuclear cell recruitment and CCR 2 expression . ^^^ Loss of MCP 1 / CCR2 signaling , as seen in CCR 2 ( / ) mice or in WT mice treated with neutralizing antibodies to MCP 1 , significantly reduced recruitment of mononuclear phagocytes following tracheal transplantation and led to attenuation of BOS . ^^^
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Radioligand binding showed that both native MCP 1 and MCP 1 SEAP competed for the same site on the surface of HEK 293 cells expressing the CCR2b chemokine receptor . ^^^
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Peripheral NK cells express the CC chemokine receptor CCR 2 , for MCP 1 and CCR 5 , for MIP 1 alpha and RANTES . ^^^
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Protein expression of the MCP 1 receptor CCR 2 did not change . ^^^
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Substantial evidence supports a causal role for monocyte chemoattractant protein 1 ( MCP 1 ) and its receptor , CCR 2 , in the recruitment of monocytes from the circulation into atherosclerotic lesions . ^^^ It generally is assumed that the magnitude of the monocyte chemotactic activity , which is initiated by the functional activation of CCR 2 by MCP 1 , is directly proportional to the concentration of the chemoattractant . ^^^ In contrast , activation of peroxisome proliferator activated receptor by synthetic ligands or components of oxidized LDL reduces monocyte CCR 2 expression and blocks chemotaxis mediated by MCP 1 . ^^^
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In conclusion , the present study highlights the major role played by MCP 1 and its counter receptor CCR 2 in the pathophysiology of IIM , and shows that the CCR 2 receptors are cell specific . ^^^ Here we have investigated the distribution of the main MCP 1 receptors CCR2A and CCR2B in IIM by polymerase chain reaction ( PCR ) , immunohistochemistry and in situ hybridization . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) , acting through its C C chemokine receptor 2 ( CCR 2 ) , has important roles in inflammation , angiogenesis , and wound repair . ^^^ The individual and combined effects of inhaled nitric oxide ( NO ) and hyperoxia on lung MCP 1 and CCR 2 in relation to lung leukocyte dynamics are unknown . ^^^ Because MCP 1 gene is up regulated by oxidants , we hypothesized that inhaled NO with hyperoxia will increase MCP 1 production and CCR 2 expression more than either gas alone . ^^^ We conclude that although hyperoxia increases MCP 1 in young piglet lungs , it also decreases CCR 2 abundance , which may limit participation of MCP 1 in alveolar macrophage recruitment . ^^^
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The expression of chemokine receptors associated with T helper ( Th ) 1 type response , CCR 1 and CCR 5 , correlated with their appropriate ligands and was the highest at the peak of AU , whereas CCR 2 , the receptor for CCL2 / MCP 1 , was present before the onset of the disease . ^^^
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In EAE protected mice , 17 beta estradiol strongly inhibited mRNA expression of the chemokines RANTES , MIP 1 alpha , MIP 2 , IP 10 , and MCP 1 , and of the chemokine receptors CCR 1 , CCR 2 and CCR 5 at both time points . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) is a chemotactic cytokine mainly acting on monocytes and T cells that elicits its biological effects by interacting with the seven transmembrane helix receptor CCR2B . ^^^ The viral chemokine binding protein vCCI thus inhibits the biological function of MCP 1 by directly masking its CCR2B receptor binding site . . ^^^
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The chemotactic activity of MCP 1 revealed a double peaked dose response curve ; one of the peaks is abolished by addition of a blocking antibody to CCR 2 , but it is insensitive to blocking of CCR 1 or CCR 3 . ^^^
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At 26 weeks postirradiation , messages encoding the chemokines BLC ( now known as Scyb 13 ) , C 10 ( now known as Scya 6 ) , IP 10 ( now known as Scyb 10 ) , MCP 1 ( now known as Scya 2 ) , MCP 3 ( now known as Scya 7 ) , MIP 1gamma ( now known as Scya 9 ) , and RANTES ( now known as Scya 5 ) and the chemokine receptors Ccr 1 , Ccr 2 , Ccr 5 and Ccr 6 were elevated in fibrosis sensitive ( C57BL / 6 ) mice . ^^^
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Previous results from this laboratory revealed the presence of high affinity saturable binding sites for monocyte chemoattractant protein 1 ( MCP 1 ) along human brain microvessels ( Andjelkovic et al . , 1999 ; Andjelkovic and Pachter , 2000 ) , which suggested that CC chemokine receptor 2 ( CCR 2 ) , the recognized receptor for this chemokine , was expressed by the brain microvascular endothelium . ^^^ To test the role of CCR 2 directly in mediating MCP 1 interactions with the brain microvasculature , we assessed MCP 1 binding activity in murine brain microvessels isolated from wild type mice and from CCR 2 ( / ) mice engineered to lack this receptor . ^^^ Results demonstrate that MCP 1 binding is greatly attenuated in microvessels prepared from CCR 2 ( / ) mice compared with wild type controls . ^^^ Furthermore , MCP 1 was shown to be internalized within wild type microvessels , but not within microvessels obtained from CCR 2 ( / ) mice , additionally demonstrating that CCR 2 is obligatory for MCP 1 endocytosis . ^^^ These results prompt consideration that MCP 1 signals may be relayed across the blood brain barrier by highly specialized interactions of this chemokine with its cognate receptor , CCR 2 , along brain microvascular endothelial cells . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Monocyte chemoattractant protein 1 ( MCP 1 ) is a C C chemokine that induces chemotaxis of a variety of lymphoid cells through its receptor CCR 2 . ^^^ CCR 2 is also expressed on B cells , and MCP 1 induces chemotaxis of normal B cells . ^^^
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Studies in animals have shown that resistance to atherosclerosis in spite of hypercholesterolemia is affected by factors such as high density lipoprotein ( HDL ) phospholipids that enhance reverse cholesterol transport , non responsiveness to induction or lack of monocyte chemotactic protein 1 ( MCP 1 ) , C C chemokine receptor 2 ( CCR 2 ) , macrophage colony stimulating factor ( MCSF ) , or vascular cell adhesion molecule 1 ( VCAM 1 ) . ^^^
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We could detect CCR 2 , a chemokine receptor that recognizes MCP 1 on Th 2 but not Th 1 lymphocytes . ^^^
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Two isoforms of human CCR 2 , the receptor for monocyte chemoattractant protein 1 ( MCP 1 ) , have been identified but their relative expression in monocytes and contribution to inflammatory responses mediated by MCP 1 remain uncertain . ^^^ The relatively abundant expression of CCR2B on the cell surface suggests a principal role of this isoform as a mediator of monocyte responses to MCP 1 in inflammation . . ^^^
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Based on these data , we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte specific blockade achieved via blockade of the MCP 1 receptor CCR 2 , was effective at reducing neointimal hyperplasia after stenting . ^^^
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In the present work we tested whether monocyte chemoattractant protein 1 ( MCP 1 ) and CCR 2 , the high affinity receptor for MCP 1 , are involved in this process . ^^^ In conclusion , MM cells express CCR 2 and are attracted by MCP 1 secreted by BMEC . ^^^
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Neutralization of RANTES ( regulated upon activation normal T cell expressed and secreted ) in the ST cell derived supernatant reduced T cell migration of all T cell lines and clones by 60 90 % , while neutralization of MCP 1 reduced the migratory capacity of CCR 2 expressing T cells by 45 80 % . ^^^
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CC chemokine receptor 2 ( CCR 2 ) is the only known functional receptor for MCP 1 . ^^^ Mice deficient in MCP 1 or CCR 2 have marked reductions in atherosclerosis . ^^^
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Recent studies demonstrated that the chemokine monocyte chemoattractant protein 1 ( MCP 1 ) / CCL2 and its receptor , CCR 2 , play important roles in various brain diseases . ^^^ In this study , using quantitative autoradiography , we studied the pharmacological properties of [ 125l ] MCP 1 / CCL2 binding in rat brain and we clearly showed the distribution of CCR 2 receptors in cerebral cortex , nucleus accumbens , striatum , amygdala , thalamus , hypothalamus , hippocampus , substantia nigra , mammillary bodies and raphe nuclei . ^^^ Our results provide the first evidence for constitutive CCR 2 receptor expression with precise neuroanatomical and cellular localizations in the brain , and its regulation during an inflammatory process , suggesting that MCP 1 / CCL2 and CCR 2 play important physiological and pathophysiological role ( s ) in the CNS . . ^^^ Four hours after an acute intraperitoneal lipopolysaccharide injection , we showed that MCP 1 / CCL2 binding was up regulated in several brain structures ; this effect took place on both CCR2B labelled neurons and astrocytes and to a lesser extent on activated microglia . ^^^
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CC chemokine receptor 2 ( CCR 2 ) , the main receptor for MCP 1 , was expressed on astrocytes , macrophages and T cells and the number of positive cells was higher in CR EAE than in acute EAE . ^^^ Collectively , these findings suggest that high expression of MCP 1 and its receptor , CCR 2 , in the CNS play important roles in relapse of EAE . . ^^^
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CCR2b , a chemokine receptor for MCP 1 , 2 , 3 , 4 , plays an important role in a variety of diseases involving infection , inflammation , and / or injury , as well as being a coreceptor for HIV 1 infection . ^^^
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In this respect , increased expression of MCP 1 and the corresponding receptor CCR 2 have been demonstrated in renal transplant rejection and coronary artery disease . ^^^ The impact of the MCP 1 2518G and CCR 2 64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11 yr period . ^^^
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To determine the potential role of MCP 1 in retrograde degeneration , the present study examined the effect of genetic deletion of MCP 1 ( MCP 1 KO or / ) or its high affinity receptor CCR 2 ( CCR 2 KO or / ) on thalamic microglial activation and neuronal cell death following aspiration lesions of the visual cortex in adult mice . ^^^ Investigation of Bcl 2 , Bax , Fas , Fas ligand ( FasL ) and activated caspase 3 , key regulators of apoptosis that can be modulated by cytokines , revealed complex alterations of mRNA and protein levels in MCP 1 ( / ) and CCR 2 ( / ) mice . ^^^ Caspase 3 activity was higher in MCP 1 ( / ) mice compared to wild type and CCR 2 ( / ) mice at 5 days after injury . ^^^
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Twenty four hours after induction of the GN , the glomerular mRNA expression of the chemokine monocyte chemoattractant protein 1 ( MCP 1 ) and the cognate chemokine receptor CCR 2 were examined by Northern blotting and RT PCR . ^^^
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To help in defining the role of MCP 1 in inflammation after SCI , we evaluated the time course of macrophage accumulation for 2 weeks following a midthoracic spinal cord contusion injury in mice lacking CCR 2 , a principal receptor for MCP 1 . ^^^
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Ccr 2 regulates the level of MCP 1 / CCL2 in vitro and at inflammatory sites and controls T cell activation in response to alloantigen . ^^^ CCR 2 , and its principle ligand MCP 1 / CCL2 , have been well documented for their ability to induce monocyte infiltration and promote the pathogenesis of rheumatoid arthritis and atherosclerosis . ^^^ In order to assess additional roles for CCR 2 , we inserted allogeneic implants into CCR 2 / and MCP 1 / mice and characterized T cell responses and the regulatory role of CCR 2 on MCP 1 expression . ^^^ The results demonstrate a marked decrease in lymphocyte infiltration in both CCR 2 / and MCP 1 / animals . ^^^ Further , whereas MCP 1 was only transiently elevated in the inflammatory fluid of WT animals , levels were sustained within the implants ( 5000pg / ml ; > 8 days ) and serum ( 243pg / ml ) of CCR 2 / mice . ^^^
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Astrocytes from different sources bind the chemokine monocyte chemoattractant factor ( MCP 1 ) , yet functional expression in these cells of CCR 2 , the major receptor for this ligand , has been a matter of controversy . ^^^ Here we show that cultured human fetal astrocytes express CCR 2 at the mRNA and protein levels , and display chemotaxis and calcium flux in response to MCP 1 . ^^^ Surface CCR 2 protein expression and MCP 1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP 1 exposure , supporting the argument that CCR 2 , and not another receptor , mediates MCP 1 ligation in these cells . ^^^
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MCP 1 induced association of focal adhesion proteins Lyn / phospho paxillin with CCR 2 was also observed by co precipitation . ^^^ Present investigations suggest that the early events in the tyrosine kinase signal transduction pathway for macrophage activation in response to MCP 1 probably involve ( 1 ) CCR 2 receptor dimerization , ( 2 ) enhanced tyrosine phosphorylation and assembly of focal adhesion complex , and ( 3 ) the activation of JAK / STAT pathway in the murine peritoneal macrophages . . ^^^
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Lastly , we present evidence that fresh patient tumor cells express mRNA for the MCP 1 receptor , CCR 2 , as do myeloma cell lines along with a second MCP 1 receptor , CCR 11 . ^^^
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However , the contribution of endothelial MCP 1 signaling via its CCR 2 receptor in monocyte adhesion to inflamed endothelium under flow is incompletely understood . ^^^ Corresponding efficacy was observed for blockade of monocyte CCR 2 receptor function by anti CCR 2 mAb or MCP 1 antagonists ( 9 76 analog ) . ^^^ Collectively , our data show an important cross talk of endothelial MCP 1 with monocyte CCR 2 effecting monocyte firm adhesion to inflamed HPAEC under physiological flow conditions . . ^^^
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Exogenous administration of the CCR 2 ligand monocyte chemoattractant protein 1 ( MCP 1 ) to the fibroblast AEC cocultures reverses the suppression mediated by CCR 2 + / + AECs but has no effect with CCR 2 / AECs . ^^^ Accordingly , AECs from CCR 2 / mice produce greater quantities of PGE ( 2 ) than do AECs from CCR 2 + / + mice , and MCP 1 inhibits AEC derived PGE ( 2 ) synthesis . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) induces monocyte migration through interaction with the MCP 1 receptor CCR 2 . ^^^
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The mRNAs for MIP 1alpha and MCP 1 , as well as their cognate receptors CCR 1 and CCR 2 , respectively , were localized in resident and infiltrating macrophages in numbers commensurate with those of F4 / 80 immunopositive macrophages in adjacent tissue sections . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To investigate the role of chemokines , we determined the blood and nerve tissue expression of monocyte chemoattractant protein 1 ( MCP 1 ) , a major chemoattractant of monocytes and activated lymphocytes , and its receptor CCR 2 in GBS and EAN . ^^^ These results suggest that MCP 1 and CCR 2 may participate to the recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS . . ^^^
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Paraffin embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP 1 , CC chemokine receptor 2 ( CCR 2 ) , TP , CD 31 , and CD 68 . ^^^ In the tumor stroma , the major source of MCP 1 , TP and CCR 2 was macrophages , and the sites of positive staining for MCP 1 , TP and CCR 2 matched in most of the myxomas . ^^^
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Differential expression of MCP 1 and its receptor CCR 2 in glucose primed human mesangial cells . ^^^ In the present study , we examined whether the ambient glucose concentration alters the expression of MCP 1 and its receptor CCR 2 in primary human mesangial cells ( HMC ) . ^^^ METHODS : MCP 1 mRNA expression was assessed by Northern blot and CCR 2 mRNA expression by RT PCR analysis . ^^^ Simultaneously , CCR 2 mRNA expression was down regulated in HMC exposed to 30 mM D glucose . 5 mM D glucose primed HMC showed a dose dependent migration towards MCP 1 that was dose dependently inhibited by pertussis toxin , the broad spectrum chemokine antagonist vMIP 2 as well as the CCR 2 receptor antagonist ( 1 8del ) MCP 1 demonstrating functional activity of MCP 1 receptor expression in primary HMC . ^^^ In accordance with the downregulatory effects of 30 mM D glucose on CCR 2 mRNA expression no migratory response towards MCP 1 was observed under these conditions . ^^^
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Pioglitazone did not reduce local expression of MCP 1 but markedly attenuated increased expression of the MCP 1 receptor C C chemokine receptor 2 ( CCR 2 ) in lesional and circulating monocytes . ^^^
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Instead , eotaxin 3 inhibits MCP 1 mediated responses , thus acting as a natural antagonist for CCR 2 . ^^^ Eotaxin 3 effects on monocytes are largely abolished when cells are pretreated with MCP 1 or CCR 2 antagonists . ^^^
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Expression of the chemokine receptors CCR 2 , specific for MCP 1 , and CXCR 1 and CXCR 2 , specific for IL 8 , were not altered by HCMV infection . ^^^
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Inhibition of beta chemokine signaling in CCR 2 / mice ( which lack the major co receptor for MCP 1 ) resulted in retarded macrophage and CD 4 T cell recruitment , enhanced eosinophil influx and a minor delay in rejection , compared with wildtype mice ; there was little effect on leukocyte infiltration in xenografts harvested from CCR 5 / mice ( lacking the co receptor for MIP 1alpha , MIP 1beta and RANTES ) . ^^^ The impeded migration of leukocytes into xenografts in CCR 2 / hosts was associated with delayed intragraft expression of MCP 1 and RANTES mRNA ; absence of MCP 1 / CCR2 mediated signaling led to enhanced intragraft expression of MCP 1 , MIP 1alpha and MIP 1beta mRNA . ^^^ These findings suggest that MCP 1 plays an important role in regulating macrophage and CD 4 T cell infiltration to xenograft sites via the CCR 2 signaling pathway . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The chemokine monocyte chemoattractant protein 1 ( MCP 1 ) and its receptor CCR 2 have been shown to play an important role in the migration and trafficking of macrophages and Th 1 effector cells in experimental autoimmune encephalomyelitis . ^^^ This study demonstrates that neither MCP 1 nor its receptor CCR 2 is required for the induction of oral tolerance . ^^^ Mice deletional for either MCP 1 or CCR 2 had suppressed cell proliferative and Th 1 responses following oral administration and immunization with myelin oligodendrocyte glycoprotein ( MOG ( 35 55 ) ) . ^^^ These results demonstrate that MCP 1 is not required for induction of oral tolerance and that MCP 1 and CCR 2 are essential for up regulation of IL 4 in tolerized mice . . ^^^
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It has recently been demonstrated in mouse models of atherosclerosis that full disease potential is dependent on several regulators of leukocyte trafficking , including the chemokine monocyte chemotactic protein 1 ( MCP 1 ) and the chemokine receptors CCR 2 and CXCR 2 . ^^^
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Chemokine receptor CCR 2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell produced monocyte chemotactic proteins MCP 1 , 2 and 3 . ^^^ In addition , we found that the monocyte chemotactic proteins ( MCPs ) MCP 1 , 2 and 3 , three chemokines acting as prominent ligands for CCR 2 , are produced by stromal cells , cultured from normal and MM BM samples . ^^^ Moreover , a blocking antibody against CCR 2 , as well as a combination of neutralizing antibodies against MCP 1 , 2 and 3 , significantly reduced the migration of human MM cells to BM stromal cell CM . ^^^
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Further studies evaluating the calcium response that is triggered upon MCP 1 interaction with its receptor , CCR 2 , indicate that this response is not altered by antisense or sense ODN treatment , thus supporting our hypothesis that PKCbeta is critical for post receptor signal transduction downstream of the immediate calcium signal . ^^^
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In summary , we propose that CCL2 / MCP 1 fulfills a novel anti inflammatory role in T cell mediated hepatitis by inhibiting CD 3 ( + ) NK1 . 1 ( + ) T cell derived IL 4 production through direct stimulation of its specific receptor CCR 2 . ^^^
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In osteoblast and myeloma cell co cultures , monocyte chemoattractant protein 1 ( MCP 1 ) mRNA was upregulated in osteoblasts from patients with severe bone disease in parallel with increased CC chemokine receptor R 2 ( CCR 2 ) expression , the ligand of MCP 1 , in the myeloma cells . ^^^
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TAK 799 ( N , N dimethyl N [ 4 [ [ [ 2 ( 4 methylphenyl ) 6 , 7 dihydro 5H benzocyclohepten 8 yl ] carbonyl ] amino ] benzyl ] tetrahydro 2H pyran 4 aminium chloride ) , a dual CCR2 / CCR5 antagonist , demonstrated high affinity for the rhesus CCR2B in competition with 125I hMCP 1 binding to the receptor ( K ( 1 ) =0 . 5 nM ) and also potently blocked the MCP 1 induced calcium mobilization mediated through the receptor . . ^^^
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In particular , M 4 M5 blasts produce MCP 1 and MIP 3alpha and also express their specific receptors ( CCR 2 and , to a lesser extent , CCR 6 ) and migrate in vitro in response to MCP 1 and MIP 3alpha and to their own supernatant . ^^^
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The present findings suggest that MCP 1 , RANTES , and IP 10 may participate in the pathogenesis of mercuric chloride induced tubulointerstitial fibrosis with mononuclear cell infiltration , via CCR 2 , CCR 1 or CCR 5 , and CXCR 3 , respectively . . ^^^
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Whereas the amplitude of calcium mobilization induced by RANTES stimulation was lower in the CCR 5 CAM than the wild type ( WT ) receptor , MCP 1 induced a higher signal in the CCR 2 CAM than in CCR 2 WT . ^^^
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Despite intensive screening , there are as yet no small molecule antagonists of the receptor of MCP 1 / CCL2 , CCR 2 . ^^^ Recent evidence from genetically modified mice indicates that MCP 1 and CCR 2 have unanticipated effects on T helper ( Th ) cell development . ^^^ However , unlike the identical phenotypes of MCP 1 / CCL2 ( / ) and CCR 2 ( / ) mice in inflammatory diseases , the phenotypes of these mice are disparate in adaptive immunity : MCP 1 stimulates Th 2 polarization , whereas CCR 2 activation stimulates Th 1 polarization . ^^^
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Whereas treatment with infectious virus induced a rapid down regulation of the CCL2 / monocyte chemoattractant protein 1 ( MCP 1 ) specific receptor CCR 2 , inactivated virus did not significantly alter CCR 2 surface expression . ^^^
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Celecoxib also significantly decreased C C family chemokine ( Rantes and MCP 1 ) mRNA expression in irradiated skin tissues , but not in tumor tissues , which was accompanied by a decrease in skin mRNA expression of both C C ( CCR 2 and CCR 5 ) and C 10 C ( CXCR 2 and CXCR 4 ) chemokine receptors . ^^^
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The chemokine monocyte chemoattractant protein 1 ( MCP 1 ) is the agonist for several chemokine receptors that belong to the GPCR superfamily , CCR 2 being the most important . ^^^ In addition , we find that internalization of CCR2B itself is not necessary for efficient MCP 1 induced activation of ERK , although a dynamin mutant partially inhibits ERK stimulation . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) and the receptor for MCP 1 , CCR 2 , play a pivotal role in the recruitment of monocytes to the subendothelium , which is the initial event in atherosclerosis . ^^^ Ang 2 significantly stimulated superoxide formation in monocytes , as measured by nitro blue tetrazolium reduction assay , as well as the chemotactic response to MCP 1 with the increased expression of CCR 2 determined by RT PCR and western blotting analysis . ^^^
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Transduced syngeneic transplanted islets showed significantly enhanced expression of multiple chemokines and receptors , including monocyte chemoattractant protein 1 ( MCP 1 ) , CC chemokine receptor 2 ( CCR 2 ) and regulated upon activation , normal T cell expressed and secreted ( RANTES ) , compared with untransduced islet grafts . ^^^ AdRSVLacZ transduced islet grafts had significant mononuclear infiltrates , and in situ hybridization demonstrated intragraft expression of MCP 1 , CCR 2 and RANTES . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 and its receptor , CCR 2 , are important mediators of macrophage accumulation and atherosclerotic plaque progression . ^^^ These data suggest that MCP 1 and CCR 2 deficiencies have distinct effects on arterial injury . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The expression of the monocyte chemoattractant protein 1 ( MCP 1 ) receptor CCR 2 by brain endothelial cells suggests that MCP 1 may have other functions than purely driving leukocyte migration into brain parenchyma during inflammation . ^^^ MCP 1 did not induce these events in brain endothelial cells prepared from mice genotype CCR 2 / . ^^^ These data are the first to strongly suggest that MCP 1 , via CCR 2 present on brain endothelial cells , contributes to increased brain endothelial permeability . . ^^^
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Interestingly , amlodipine prevented the L NAME induced increase in MCP 1 receptor CCR 2 expression in circulating monocytes . ^^^ The anti inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP 1 but also by the decrease in CCR 2 in circulating monocytes . ^^^ Inhibition of the MCP 1 to CCR 2 pathway may represent novel anti inflammatory actions of amlodipine beyond blood pressure lowering . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
C C chemokine receptor 2 ( CCR 2 ) is a receptor for chemoattractant protein 1 ( MCP 1 ) and associated with infiltrating lymphocytes in chronic active multiple sclerosis ( MS ) lesions . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The chemokine receptors CCR 5 , CCR 2 , and CCR 3 and their ligands , RANTES , MCP 1 , MCP 2 , and MIP 1alpha , are involved in the immune responses and the selective recruitment of lymphocytes to the liver in HCV infection . ^^^
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We examined isolated murine type 2 alveolar epithelial cells ( AECs ) for expression of CC chemokine receptor 2 ( CCR 2 ) and functional consequences of the binding of the main CCR 2 ligand monocyte chemoattractant protein 1 ( MCP 1 ) . ^^^ We found that primary AECs bound MCP 1 and expressed CCR 2 mRNA . ^^^ These cells demonstrated functional consequences of CCR 2 expression with migration in response to MCP 1 in chemotaxis / haptotaxis assays . ^^^ Primary AECs cultured from mice lacking CCR 2 did not respond to MCP 1 . ^^^ CCR 2 MCP 1 interactions may be important in the process of reepithelialization after lung injury . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Astrocytes suffering caveolin 1 loss showed diminished ability to down modulate and internalize the MCP 1 receptor ( CCR 2 ) in response to exposure to this chemokine and also demonstrated significantly reduced capacity to undergo chemotaxis and calcium flux when MCP 1 stimulated . ^^^
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Gammadelta T cells express MCP 1 receptor CCR 2 . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) attracts monocytes bearing the chemokine receptor CCR 2 . ^^^
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Effects of bacterial cell wall components ( PAMPs ) on the expression of monocyte chemoattractant protein 1 ( MCP 1 ) , macrophage inflammatory protein 1alpha ( MIP 1alpha ) and the chemokine receptor CCR 2 by purified human blood monocytes . ^^^ The present study was designed to study the effects of five different bacterial cell wall components ( PAMPs ) on the production of MCP 1 and MIP 1alpha and the expression of CCR 2 by highly purified human blood monocytes . ^^^ We conclude that MCP 1 and MIP 1alpha as well as the MCP 1 receptor CCR 2 will be substantially regulated upon monocyte contact with various cell wall components ( PAMPs ) from Gram negative and Gram positive bacteria as well as from mycobacteria . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Urinary CCL2 / MCP 1 , but not CX3CL1 / fractalkine , correlated with glomerular macrophage accumulation ( r = 0 . 936 , P < 0 . 01 ) and glomerular CCR 2 mRNA expression ( r = 0 . 965 , P < 0 . 01 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
MCP 1 , which signals via the CC chemokine receptor 2 ( CCR 2 ) , is induced in lung fibrosis that is accompanied by mononuclear cell recruitment and activation of lung fibroblasts . ^^^
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Thus we postulated that the genes encoding CCR 5 and CCR 2 , which are the receptors for RANTES and MCP 1 respectively , could be good candidate genes for the disease . ^^^
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Rat aortic MCP 1 and its receptor CCR 2 increase with age and alter vascular smooth muscle cell function . ^^^ Because arterial angiotensin 2 , which induces MCP 1 expression , increases with age , we hypothesized that aortic MCP 1 and its receptor CCR 2 are also upregulated and affect VSMC properties . ^^^ METHODS AND RESULTS : Both MCP 1 and CCR 2 mRNAs and proteins increased in old ( 30 month ) versus young ( 8 month ) F344xBN rat aortas in vivo . ^^^ Cellular MCP 1 and CCR 2 staining colocalized with that of alpha smooth muscle actin in the thickened aortas of old rats and were expressed by early passage VSMCs isolated from old aortas , which , relative to young VSMCs , exhibited increased invasion , and the age difference was abolished by vCCI , an inhibitor of CCR 2 signaling . ^^^
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OBJECTIVES : To investigate whether plasma concentrations of monocyte chemoattractant protein 1 ( MCP 1 ) and the gene expression of its receptor on the monocyte cell surface CCR 2 were elevated above normal in subjects with asymptomatic , isolated hypercholesterolaemia and if statin treatment could influence this cytokine . ^^^ No difference in plasma MCP 1 levels or CCR 2 gene expression was seen between the groups at baseline , nor were there any differences in plasma concentrations of CRP . ^^^ Treatment did not significantly affect the levels of MCP 1 or CCR 2 gene expression , nor was CRP affected by treatment with pravastatin . ^^^ CONCLUSIONS : Our study does not support the view that MCP 1 plasma levels and CCR 2 gene expression in circulating monocytes are directly responsible for the monocyte recruitment into the arterial intima in patients with severe asymptomatic hypercholesterolaemia . ^^^
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Differential expression of beta chemokines MCP 1 and RANTES and their receptors CCR 1 , CCR 2 , CCR 5 in acute rejection and chronic allograft nephropathy of human renal allografts . ^^^ METHODS : In 24 renal transplant biopsies with AR ( n = 15 ) and CAN ( n = 9 ) , the expression of MCP 1 and RANTES , their receptors CCR 1 , CCR 2 , and CCR 5 and the infiltration with monocytes / macrophages and T cells were studied . ^^^ Biopsies with CAN revealed a lower expression of MCP 1 , RANTES , CCR 1 , CCR 2 and CCR 5 in tubulointerstitial cells , and a significantly lower infiltration with MRP 14 positive monocytes / macrophages than biopsies with AR . ^^^ In AR , MCP 1 and CCR 1 showed a lower expression compared to RANTES , CCR 2 , and CCR 5 . ^^^ CONCLUSIONS : The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection , the lower but detectable expression of MCP 1 , RANTES , CCR 1 , CCR 2 and CCR 5 in CAN , and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts . ^^^
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METHODS : Paraffin embedded sections of tissue samples taken from 56 patients with esophageal SCC after curative surgery were immunohistochemically stained for MCP 1 , CC chemokine receptor 2 ( CCR 2 ) , and thymidine phosphorylase ( TP ) . ^^^ There was a significant correlation between the expression of MCP 1 in cancer cells and of CCR 2 in stromal cells . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) controls monocyte mediated inflammation through its receptor , CCR 2 . ^^^
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METHOD : An NH ( 2 ) terminal deletion mutant of the MCP 1 gene , 7ND , was injected into skeletal muscles of MRL / lpr mice with advanced stage nephritis to blockade MCP 1 and its receptor ( CCR 2 ) signalling pathway . ^^^
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The intracellular Ca ( 2+ ) concentration and the chemotactic activity increased in 9 CRA treated cells in response to the CCR 1 dependent chemokines Lkn 1 , MIP 1alpha , and RANTES , and the CCR 2 specific chemokine MCP 1 . ^^^
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To identify the elements of two chemokines [ monocyte chemoattractant protein 1 ( MCP 1 ) and eotaxin ] that control their differential recognition by their respective receptors ( CCR 2 and CCR 3 ) , we have studied the receptor interactions of MCP 1 eotaxin chimeras . ^^^
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CCR 1 and CCR 2 , which are the receptors for MCP 1 and RANTES , were also expressed at constitutively high levels while others were not detectable . ^^^
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CONCLUSIONS : The MCP 1 / chemokine receptor 2 ( CCR 2 ) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy . ^^^
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Based on these findings , we prepared plasmid DNAs encoding the binding site of CCR 2 and CXCR 3 , which are receptors for MCP 1 and IP 10 , respectively . ^^^
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We analyzed the prognostic factors of ESRF in the first renal biopsies ; these factors included presence of tubulointerstitial lesions and foam cells , as well as expression of CD 68 , monocyte chemoattractant protein 1 ( MCP 1 ) , its cognate receptor chemokine receptor 2 ( CCR 2 ) and alpha smooth muscle actin . ^^^ RESULTS : The patients who developed ESRF showed higher percentages of glomerular segmental sclerosis , interstitial MCP 1 expression , CCR 2 or CD 68 positive monocyte / macrophages and foam cells in the interstitium , and these proved on multivariate analysis to be independent risk factors for ESRF . ^^^
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MCP 1 binds to the chemokine receptor CCR 2 which is known to be expressed on monocytes and macrophages . ^^^ Thus MCP 1 and CCR 2 interaction is likely of importance for the monocyte / macrophage trafficking of inflammatory skin disorders . . ^^^
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These expression levels of TGFbeta and MCP 1 mRNA correlated with the SLEDAI score ( TGFbeta r = 0 . 71 , P < 0 . 001 ; MCP 1 r = 0 . 72 , P < 0 . 001 ) , and also significantly correlated with the histologic activity index ( TGFbeta r = 0 . 487 , P = 0 . 004 ; MCP 1 r = 0 . 357 , P = 0 . 038 ) . ^^^
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We investigated mutations in the monocyte chemoattractant protein 1 ( MCP 1 ) and CCR 2 genes , which are known to control aspects of these pathways , to ascertain whether they are involved in atherogenesis in these patients . ^^^ MCP 1 2518G and CCR 2 64I polymorphisms were determined in the HIV group and in a population based control group ( n=348 ) . ^^^
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To determine whether the MCP 1 mediated response occurs through its receptor , CC chemokine receptor 2 ( CCR 2 ) , we induced hindlimb ischemia in mice lacking the receptor for MCP 1 ( CCR 2 / ) and measured limb blood flow recovery , collateral artery development , and monocyte and macrophage recruitment . ^^^ Intercellular adhesion molecule 1 and MCP 1 mRNA levels were higher in the thigh muscle of CCR 2 / mice than in wild type mice ( 5 . 5 fold and 42 . 3 fold induction operated to unoperated vs 2 . 6 fold and 6 . 1 fold induction operated to unoperated , respectively ) . ^^^ Our results show that MCP 1 signaling through CCR 2 is not required for physiologic arteriogenesis in response to severe hindlimb ischemia . ^^^ ICAM 1 upregulation may substitute for MCP 1 signaling through CCR 2 in order to allow normal arteriogenesis in CCR 2 / mice . . ^^^
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Chemokines ( RANTES and MCP 1 ) and chemokine receptors ( CCR 2 and CCR 5 ) gene polymorphisms in Alzheimer ' s and Parkinson ' s disease . ^^^ We examined whether DNA polymorphisms at the genes encoding chemokines MCP 1 ( 2518 A / G ) and RANTES ( 403 A / G ) , and chemokine receptors 5 ( CCR 5 , Delta 32 ) and 2 ( CCR 2 , V64I ) , were associated with the risk and / or the clinical outcome of LOAD and PD . ^^^
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Expression of the MCP 1 receptor CCR 2 in neurosphere cultures was verified by RT PCR and immunofluorescence microscopy . ^^^
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Administration of anti MCP 1 antibody prevented infiltration of mononuclear cells bearing the MCP 1 receptor CCR 2 in mice with viral myocarditis . ^^^
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However , we observed that CCR 5 specific ligands that are unable to compete for monocyte chemoattractant protein ( MCP 1 ) binding on cells expressing CCR2b alone efficiently prevented MCP 1 binding when CCR 5 and CCR2b were coexpressed . ^^^ Similar observations were made for the CCR2b selective ligand MCP 1 that competed efficiently for macrophage inflammatory protein 1beta binding on cells expressing both receptors . ^^^
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Monocyte chemoattractant protein 1 ( MCP 1 ) , acting through its receptor CCR 2 , appears to play an early and important role in the recruitment of monocytes to atherosclerotic lesions and in the formation of intimal hyperplasia after arterial injury . ^^^ Because of their critical roles in monocyte recruitment in vascular and nonvascular diseases , MCP 1 and CCR 2 have become important therapeutic targets , and efforts are underway to develop potent and specific antagonists of these and related chemokines . . ^^^
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Further , MCP 1 from PAP lung suppresses CCR 2 expression in vitro , suggesting that in PAP , MCP 1 participates in an autocrine regulatory network in vivo . . ^^^
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Site directed mutagenesis of CCR 2 identified amino acid residues in transmembrane helices 1 , 2 , and 7 important for MCP 1 binding and biological functions . ^^^ Monocyte chemotactic protein 1 ( MCP 1 ) binds its G protein coupled seven transmembrane ( TM ) receptor , CCR2B , and causes infiltration of monocytes / macrophages into areas of injury , infection or inflammation . ^^^ MCP 1 treatment of HEK 293 cells caused lamellipodia formation only when they expressed CCR2B . ^^^
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Absence of CCR 2 diminishes any effect of MCP 1 on BBB permeability in vitro and in vivo . ^^^ The permeability surface area product for FITC albumin after 3 days exposure to MCP 1 was 0 . 096+ / 0 . 006 and 0 . 032+ / 0 . 007 microL / g min , in CCR2+ / + and CCR 2 / mice , respectively ( P < 0 . 001 ) . ^^^
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The prominence of the CCR 2 receptors further underlines the importance of the interaction with their ligand MCP 1 in the immunopathogenesis of IIM and puts CCR2B forward as a potential target for future therapeutic intervention . . ^^^ In contrast to an earlier report , we found CCR2B to be the most prominent MCP 1 receptor on inflammatory cells in IIM , especially in PM and sIBM . ^^^
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Simvastatin treated monocytes showed little chemotaxis movement in response to monocyte chemoattractant protein 1 ( MCP 1 ) , a specific CCR 2 ligand . ^^^
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Our results show that NHA treated with morphine showed significant downregulation of the gene expression of beta chemokines , MCP 1 , and MIP 1 beta , while reciprocally upregulating the expression of their specific receptors , CCR2b , CCR 3 , and CCR 5 as detected by real time quantitative PCR . ^^^
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CROSS N ( 2 ) E 3 ( 2 ) binds to the CCR 2 ligand monocyte chemoattractant protein 1 ( MCP 1 ) with a dissociation equilibrium constant of 1 . 1 + / 0 . 1 microM but does not bind to the cognate chemokines of the receptor CCR 3 ( eotaxin 1 , 2 , and 3 ) . ^^^
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Levels of monocyte chemoattractant protein ( MCP ) 1 were increased postoperatively , correlating with a reduction of CCR 2 expression and an increase of CD11b expression on monocytes , suggesting monocyte activation by MCP 1 . ^^^
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We observed an early up regulated expression of IP 10 , MCP 1 , MCP 3 , MIP 1alpha , MIP 2 , and CCR 2 which was reversed within 36 h . ^^^
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In CCR 2 ( / ) mice or WT mice treated in vivo with antibodies to either MCP 1 or MIP 1 alpha , MPO activity was greatly attenuated in CLP animals . ^^^ In CLP mice , increased serum IL 6 levels were found to be dependent on CCR 2 , MCP 1 , and MIP 1 alpha . ^^^
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Synthetic MCP 1 and the analogs were comparable to recombinant MCP 1 in competition radio ligand binding to CCR 2 receptors on THP 1 cells , and MCP 1 induced , calcium mobilization and chemotaxis assays . . ^^^
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Recombinant rabbit CCR 2 expressed as stable transfectants in U 937 cells binds radiolabeled 125I mouse JE ( murine MCP 1 ) with a calculated Kd of 0 . 1 nM . ^^^ In competition binding assays , binding of radiolabeled mouse JE to rabbit CCR 2 is differentially competed by human MCP 1 , 2 , 3 and 4 , but not by RANTES , MIP 1alpha or MIP 1beta . ^^^ U 937 / rabbit CCR 2 stable transfectants undergo chemotaxis in response to both human MCP 1 and mouse JE with potencies comparable to those reported for human CCR2b . ^^^ CONCLUSION : In this study , we report the cloning of rabbit CCR 2 and demonstrate that this receptor is a functional chemotactic receptor for MCP 1 . . ^^^
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These results indicate that the binding of increased MCP 1 induced by endogenous NO blockade to CCR 2 mediated the enhancement of Ca2+ influx only when monocytes adhered to ECs , which upregulated TF expression in ECs triggered by monocyte adhesion . ^^^
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Preceding the build up of atherosclerotic lesions , AngII exposure increased mRNA expression and immunostaining of monocyte chemoattractant protein 1 ( MCP 1 ) and its receptor , CCR 2 . ^^^
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Moreover , the in vivo elevated levels of interleukin 2 ( IL 2 ) and monocyte chemoattractant protein 1 ( MCP 1 ) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR 2 pathway in aberrant NK cell retention at chronic inflammatory sites . . ^^^
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Monocyte chemotactic protein 1 ( MCP 1 ) promotes collagen synthesis and deletion of the MCP 1 receptor CCR 2 protects from pulmonary fibrosis in ILD mouse models . ^^^
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METHOD : An NH 2 terminal deletion mutant of the MCP 1 gene ( 7ND ) was injected into the skeletal muscles of MRL / Ipr mice with advanced stage nephritis to suppress MCP 1 and its receptor ( CCR 2 ) signaling pathway . ^^^
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Binding of ( 125 ) 1 labeled MCP 1 to its receptor ( CCR 2 ) on THP 1 human monocytic cells was not affected by EtOH treatment . ^^^
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Using untreated A7r5 cells , two MCP 1 receptors , CCR 2 and CCR 4 , were detected and MCP 1 secretion was significantly increased by stimulation with platelet derived growth factor . ^^^
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No change in DIO susceptibility and macrophage accumulation in adipose tissue were observed in CCR 2 knockout mice , which lack the MCP 1 receptor CCR 2 . ^^^
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Constitutive expression of CCR 2 chemokine receptor and inhibition by MCP 1 / CCL2 of GABA induced currents in spinal cord neurones . ^^^ Cultured neurones stimulated with Monocyte Chemoattractant Protein 1 ( MCP 1 ) / CCL2 , the best characterized CCR 2 agonist , showed activation of the Akt pathway . ^^^ These data constitute the first demonstration of a modulatory role of MCP 1 on GABAergic neurotransmission and contribute to our understanding of the roles of CCR 2 and MCP 1 / CCL2 in spinal cord physiology , in particular with respect to nociceptive transmission , as well as the implication of this chemokine in neuronal adaptation or dysfunction during neuropathy . . ^^^
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Moreover , we examined the effect of CysLTs on the expression of beta chemokine receptor 2B ( CCR2B ) as the receptor of MCP 1 by Western blot analysis . ^^^ PCR demonstrated that CysLTs increased MCP 1 mRNA expression in THP 1 cells , and Western blotting showed that CysLTs increased the expression of CCR2B in THP 1 cells . ^^^ Moreover , we demonstrated that pranlukast , a CysLT 1 receptor antagonist , blocked MCP 1 production by CysLTs in THP 1 cells almost completely , and partially inhibited MCP 1 release by CysLTs in peripheral blood CD14+ monocytes / macrophages and CCR2B expression by CysLTs in THP 1 cells . ^^^ CONCLUSION : CysLTs induce MCP 1 and increase CCR2B expression in human monocytes / macrophages . . ^^^
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One chemokine , monocyte chemoattractant protein 1 ( MCP 1 ) , in the presence of its cognate receptor , the beta chemokine receptor 2 ( CCR 2 ) , produces neural activity in dissociated neuronal cultures of neonatal dorsal root ganglion ( DRG ) neurons . ^^^ In addition , the preferred CCR 2 ligand , MCP 1 , was up regulated by POD 5 in both compressed L4 / L5 and noncompressed L3 / L6 DRG neurons . ^^^
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Induction of chemokines and chemokine receptors CCR2b and CCR 4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP 1 and RANTES . ^^^ Since CCR2b and CCR 4 are MCP 1 receptors , these data support the existence of an MCP 1 autocrine loop in human osteoclasts differentiated using RANKL . . ^^^
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Synovial cells and mononuclear inflammatory cells expressed both MCP 1 and its receptor , CCR 2 . ^^^ Increased expression of MCP 1 and CCR 2 in knee joints of AIA rats suggests a role for this cytokine in triggering the mechanisms involved in the pathogenesis of knee joint after ankle erosion . . ^^^
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We report that PF express functional receptors for MCP 1 that are distinct from the receptor CCR 2 . ^^^
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In contrast , CCR2a and CCR2b , as well as D 6 and US 28 ( other potential receptors of MCP 1 ) , were not detectable in SSc and normal fibroblasts , and their expression was not induced by platelet derived growth factor , IL 1beta , or IL 4 . ^^^
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The recruitment and activation of Mo are regulated by C C chemokines , especially monocyte chemoattractant protein 1 [ ( MCP 1 ) / CC chemokine ligand 2 ] , which interacts with CC chemokine receptor 2 ( CCR 2 ) . ^^^ The effect of MCP 1 on the expression of MCP 1 , CCR 2 , transforming growth factor beta 1 ( TGF beta 1 ) , and type 1 collagen in circulating human CD 14 positive Mo was investigated . ^^^ Similarly , the expression of MCP 1 and CCR 2 was enhanced by the stimulation with MCP 1 in dose and time dependent manners . ^^^
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Analysis of corneal inflammation induced by cauterisation in CCR 2 and MCP 1 knockout mice . ^^^ The corneas were cauterised with silver nitrate in CCR 2 knockout ( KO ) mice , MCP 1 KO mice , and control mice . ^^^ RESULTS : After cauterisation both CCR 2 KO and MCP 1 KO mice showed the same levels of corneal oedema and opacity as control mice . ^^^ Flow cytometry revealed that in control mice most of the infiltrating cells were neutrophils and macrophages , whereas in both CCR 2 KO mice and MCP 1 KO mice , the number of macrophages infiltrating the cornea were markedly reduced . ^^^ However , prominent infiltrates of neutrophils were still observed in the cornea in CCR 2 KO mice and MCP 1 KO mice . ^^^
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These compounds inhibited the binding of MCP 1 to CCR 2 ( CHO membrane ) with IC 50 values of 0 . 8 to 9 microM and exhibited good activity in a whole cell assay using MCP 1 and human monocytes with IC 50 ' s ranging from 4 9 microM . ^^^
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Induction of MCP 1 , CCR 2 , and iNOS expression in THP 1 macrophages by serum of children late after Kawasaki disease . ^^^ Given the potential roles of monocyte chemoattractant protein 1 ( MCP 1 ) , chemokine receptor CCR 2 , and inducible nitric oxide synthase ( iNOS ) in atherogenesis , we sought to determine whether serum obtained from children late after KD would induce expression of these genes in macrophages in vitro . ^^^ Expression of MCP 1 , CCR 2 , and iNOS mRNA in THP 1 macrophages in the presence of patient and control serum was quantified as a ratio to beta actin mRNA and expressed as a percentage of control . ^^^ The magnitude of induction of MCP 1 , CCR 2 , and iNOS or in combinations correlated positively with serum high sensitivity C reactive protein ( hs CRP ) , and low density lipoprotein ( LDL ) cholesterol levels and negatively with high density lipoprotein ( HDL ) cholesterol level . ^^^ In conclusion , the serum of patients with a history of KD induces expression of MCP 1 , CCR 2 , and iNOS in THP 1 macrophages in vitro . ^^^
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CONCLUSIONS : Overall , these findings suggest that the chemokines MCP 1 and MIP 1alpha , acting through their receptors CCR 2 and CCR 5 , are important in the induction of EAM and that inhibition of MCP 1 with 7ND gene transfection significantly reduced disease severity . ^^^
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However , the gene expression changes caused by signal transduction , triggered by MCP 1 binding to its receptor CCR 2 , and their possible role in the development of IHD are not understood . ^^^ We present evidence that MCP 1 binding to CCR 2 induces a novel transcription factor ( MCP induced protein [ MCPIP ] ) that causes cell death . ^^^ MCPIP production induced by MCP 1 binding to CCR 2 in the cardiomyocytes is probably involved in the development of IHD in this murine model . ^^^
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MCP 1 induced proliferation and invasion of CaP cells and this was abolished partially either by CCR 2 antagonist or PI 3 Kinase inhibitor . ^^^
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BACKGROUND : Monocyte chemoattractant protein 1 ( MCP 1 ) and its major receptor , CC chemokine receptor 2 ( CCR 2 ) , have been shown to contribute to left ventricular remodeling after myocardial infarction . ^^^
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CC Chemokine receptor 2 ( CCR 2 ) , the cognate MCP 1 receptor , has been recently demonstrated in human mesangial cells ( HMCs ) . ^^^ We tested whether MCP 1 binding to CCR 2 affects ICAM 1 expression in HMCs and , secondly , if stretch induced ICAM 1 is mediated by MCP 1 via an autocrine mechanism . ^^^ Serum deprived HMCs were exposed to either rh MCP 1 ( 0 . 1 1 10 50 100 ng / ml ) or mechanical stretch in the presence and in the absence of RS 102895 , a specific CCR 2 inhibitor . ^^^ Stretch induced ICAM 1 expression was not altered by CCR 2 blockade and stretch significantly reduced CCR 2 mRNA and protein expression via an MCP 1 independent mechanism . ^^^ Stretch induced CCR 2 downregulation may favour MCP 1 paracrine activity . . ^^^
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Caval thrombi were also formed in CCR 2 / and MCP 1 / mice and in wild type mice transfected with an adenoviral construct expressing a broad spectrum CC receptor antagonist . ^^^ Deletion of CCR 2 or blockade of all CC chemokines inhibited both monocyte recruitment ( P < . 05 ) and thrombus resolution ( P < . 01 ) , but knocking out MCP 1 had no effect . ^^^
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Whole cell RNA was isolated and chemokine ( IL 8 , CCL2 / MCP 1 , CXCL10 / IP 10 and CCL5 / RANTES ) and chemokine receptor ( CCR 2 and CCR 5 ) expression was tested by quantitative PCR . ^^^
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Eotaxin 3 , a natural CCR 2 antagonist , was released within 1 h and may delay mononuclear cell responses to MCP 1 . ^^^
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The expression levels of CCR 2 , CD 36 , and CD 68 on monocytes were significantly increased in diabetic patients and were more upregulated by MCP 1 stimulation . ^^^ Our data suggest that elevated serum MCP 1 levels and increased monocyte CCR 2 , CD 36 , CD 68 expression correlate with poor blood glucose control and potentially contribute to increased recruitment of monocytes to the vessel wall in diabetes mellitus . . ^^^
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The Fab blocks CCR 2 receptor binding to MCP 1 through an adjacent but distinct binding site . ^^^
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Both receptors are members of the G protein coupled , seven transmembrane domain family of receptors and are most closely related to the human monocyte chemoattractant protein 1 receptor . ^^^
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The hypothesis that the structural determinants for CC chemokine / CCR5 interactions and CCR 5 HIV 1 fusion co receptor activity may be shared was confirmed by two novel observations : first , the fusion activity supported by two hybrid receptors could be inhibited by both RANTES and monocyte chemoattractant protein 1 , chemokines specific to CCR 5 and CCR2B , respectively ; and second , the chemokine specificity for inhibition of envelope mediated cell fusion matched the agonist profile of these hybrid receptors . ^^^
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Expression of both MCP 1 and its receptor CCR 2 was evaluated in circulating ECs and macrophages by flow cytometry and real time reverse transcriptase polymerase chain reaction ( RT PCR ) , while gene variants of MCP 1 were revealed by PCR . ^^^
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CCR 2 receptor is expressed in glomerular podocytes of Alport mice , suggesting MCP 1 activation of CCR 2 on podocytes may underlie induction of MMP 12 . ^^^
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The functional involvement of MCP 1 in vein graft remodeling is demonstrated by blocking the MCP 1 receptor CCR 2 using 7ND MCP 1 . 7ND MCP 1 gene transfer resulted in 51 % reduction in IH in the mouse model , when compared with controls . ^^^
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Antagonist 37 had a CCR 2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP 1 induced monocyte chemotaxis ( IC 50 of 41 nM ) . . ^^^
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IL 2 and IFN gamma were significantly reduced in early CCR 2 / thrombi , whereas MCP 1 was significantly increased , and Th 2 lymphokines were unaffected . ^^^
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Severe hindlimb ischemia stimulated MCP 1 expression that was strongly enhanced by FGF 2 gene transfer , and a blockade of MCP 1 activity via a dominant negative mutant as well as a deficiency of its functional receptor CCR 2 resulted in the diminished recovery of blood flow attributable to adaptive and therapeutic neovascularization . ^^^
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Monocyte chemoattractant protein 3 , but not monocyte chemoattractant protein 2 , is a functional ligand of the human monocyte chemoattractant protein 1 receptor . ^^^
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Signal transduction and ligand specificity of the human monocyte chemoattractant protein 1 receptor in transfected embryonic kidney cells . ^^^
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DNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor . ^^^
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In this study , we explored the relative contribution of the monocyte chemoattractant protein 1 receptor , CCR 2 , in the pulmonary response to A . fumigatus conidia . ^^^
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To obtain insights into this potential mechanism , we made use of mice deficient in the CC chemokine receptor 2 ( CCR 2 ) , the receptor for monocyte chemoattractant protein 1 . ^^^
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To investigate the role of the carboxyl terminal region ( 52 amino acids ) of the monocyte chemoattractant protein 1 receptor ( CCR2B ) in chemotaxis , we created a series of mutants and expressed them in a murine pre B lymphocyte cell line . ^^^ Upon incubation with monocyte chemoattractant protein 1 , CCR2B underwent rapid and extensive internalization , and this was impaired progressively as the carboxyl tail was truncated from 52 to 8 amino acids . ^^^
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Instead , direct cell cell contact between macrophages and cells engineered to express CD40L ( also known as CD 154 ) resulted in the production of large amounts of macrophage inflammatory protein 1alpha and 1beta , and RANTES ( all ligands for CCR 5 ) , and monocyte chemoattractant protein 1 ( a ligand for CCR 2 ) . ^^^
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Cloning and functional characterization of the 5 ' flanking region of the human monocyte chemoattractant protein 1 receptor ( CCR 2 ) gene . ^^^ The human monocyte chemoattractant protein 1 receptor designated hCCR 2 is an essential co receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein 1 , a member of the family of C C chemokines that mediate monocyte chemotaxis . ^^^
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The chemokine monocyte chemoattractant protein 1 induces functional responses through dimerization of its receptor CCR 2 . ^^^
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In paralyzed control mice , the SC had increased cellular infiltration and strong expression of the chemokines RANTES , IFN inducible 10 kDa protein , and monocyte chemoattractant protein 1 and the cognate chemokine receptors CCR 1 , CCR 2 , and CCR 5 , with lower expression of macrophage inflammatory protein ( MIP ) 1alpha , MIP 1beta , and MIP 2 ; whereas brain had less infiltration and a lower expression of a different pattern of chemokines and receptors . ^^^
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Analysis of single cell calcium transients revealed a robust response to stromal derived factor 1alpha ( CXCR 4 ) and melanocyte growth stimulating activity ( CXCR 2 ) , and variable response to monocyte chemoattractant protein 1 ( CCR 2 ) or interferon gamma inducible protein 10 ( CXCR 3 ) . ^^^
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Although the C C chemokine monocyte chemoattractant protein 1 and its receptor , CCR 2 , have been implicated in atherosclerosis , the role of the classic C 10 C chemokine , interleukin 8 ( KC / growth related oncogene alpha in mice ) and its receptor CXCR 2 has not been studied in the pathogenesis of atherosclerosis . ^^^
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We have recently shown that mice with a targeted disruption of CCR 2 , the receptor for monocyte chemoattractant protein 1 , have markedly impaired recruitment of macrophages to sites of inflammation . ^^^
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Homocysteine stimulates the expression of monocyte chemoattractant protein 1 receptor ( CCR 2 ) in human monocytes : possible involvement of oxygen free radicals . ^^^
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Therefore , we have investigated the contribution of the main monocyte chemoattractant protein 1 chemokine receptor , CCR 2 , to the fibrotic disease process . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
CCR 2 is the receptor of monocyte chemoattractant protein 1 , and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR 2 KO mice . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Role of monocyte chemoattractant protein 1 and its receptor , CCR 2 , in the pathogenesis of bleomycin induced scleroderma . ^^^ These data suggest that monocyte chemoattractant protein 1 and CCR 2 signaling plays an important part in the pathogenesis of bleomycin induced scleroderma . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Our study identifies eight genes ( IL 1beta , IL 1RA , macrophage inflammatory protein 1beta , monocyte chemoattractant protein 1 , CC chemokine receptor ( CCR ) 1 , CCR 2 , CCR 5 , and F4 / 80 ) that are highly expressed in all of our experimental groups . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Transforming growth factor beta and its signaling pathway ( JAK kinase and STAT 6 , Smad2 / 3 , and Smad 7 ) appear to play a central role in the development of fibrosis as well as monocyte chemoattractant protein 1 , CCR 2 , platelet derived growth factor C , and excessive apoptosis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The regulation of BLT 1 mRNA and receptor protein expression was similar to the regulation of the monocyte chemoattractant protein 1 chemokine receptor , CC chemokine recptor 2 ( CCR 2 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We have previously shown that the expression of monocyte CCR 2 , the receptor for monocyte chemoattractant protein 1 , is induced by plasma cholesterol . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
At the end of each experimental period , surface FXa and thrombin receptors ( EPR 1 and PAR 1 , 2 , and 4 ) and CCR 2 ( monocyte chemoattractant protein 1 receptor ) gene expression in isolated PBMC were examined . the ability of dialytic membranes to activate protein tyrosine kinases and the stress activated kinase JNK and to modulate the generation of terminal complement complex ( TCC ) was also investigated . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Furthermore , a number of genes were differentially expressed more than 2 fold in response to treatment , including a downregulation of the proinflammatory mediators tumor necrosis factor ( TNF ) beta , TNF receptor , neurotrophin 3 growth factor receptor , and monocyte chemoattractant protein 1 receptor . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We report that A / J mice immunized with mc TnI developed severe inflammation of the myocardium with increased expression of inflammatory chemokines RANTES ( regulated on activation normal T cell expressed and secreted ) , monocyte chemoattractant protein 1 , macrophage inflammatory protein ( MIP ) 1alpha , MIP 1beta , MIP 2 , T cell activation gene 3 , and eotaxin and chemokine receptors CCR 1 , CCR 2 , and CCR 5 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR 2 ( monocyte chemotactic protein 1 receptor ) is also regulated by LPS . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Here we report that superantigen stimulation of human peripheral blood monocytes results in a rapid , dose dependent , and specific down regulation of chemokine ( macrophage inflammatory protein 1alpha ( MIP 1alpha ) , monocyte chemotactic protein 1 and MIP 1beta ) binding sites ( e . g . , CCR 1 , CCR 2 , and CCR 5 ) , which correlates with a concomitant hyporesponsiveness of human monocytes to these CC chemokine ligands . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
We have shown previously that in human monocytes , bacterial lipopolysaccharide , IL 1 , and tumor necrosis factor alpha induce a rapid down regulation of the monocyte chemotactic protein 1 receptor CCR 2 ( CC chemokine receptor 2 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
In contrast to other chemokines , such as monocyte chemotactic protein 1 ( CC chemokine receptor 2 [ CCR 2 ] ) , macrophage inflammatory protein 1beta ( CCR 5 ) , liver and activation regulated chemokine ( LARC [ CCR 6 ] ) , Epstein Barr virus induced molecule 1 ligand chemokine ( ELC [ CCR 7 ] ) , and IP 10 ( CXCR 3 ) , SDF 1 stimulates the prolonged activation of protein kinase B and extracellular signal regulated kinase ( ERK ) 2 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
The Ab MC 21 ( anti CCR 2 ) reduced the activity of murine monocyte chemotactic protein 1 by 95 % , whereas the Ab MC 68 ( anti CCR 5 ) blocked over 99 % of the macrophage inflammatory protein 1alpha and RANTES activity . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Whereas freshly harvested monocytes were strongly attracted by monocyte chemotactic protein 1 ( MCP 1 ) , a specific ligand for CCR 2 , only a weak response was observed to macrophage inflammatory protein 1alpha ( MIP 1alpha ) , which binds to CCR 1 and CCR 5 . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
OBJECTIVE : Studies in mice have shown that genetic disruption of monocyte chemotactic protein 1 or its receptor , the C C chemokine receptor 2 ( CCR 2 ) , inhibits atherosclerosis , but few data exist in humans to suggest that the monocyte chemotactic protein 1 CCR 2 interaction is important in atherogenesis . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
RESULTS : Early monocyte activation was demonstrated by changes of the expression of the chemokine receptor CCR 2 , which was inversely correlated with plasma levels of monocyte chemotactic protein 1 ( rho = 0 . 54 , P = . 002 ) . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Under these conditions , the gene expressions of monocyte chemotactic protein 1 and its receptor , CCR 2 , were not significantly different in the control and diseased regions of both AAA and CAS . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
Peak plasma concentrations of the CCR 2 ligand monocyte chemotactic protein 1 and of tumor necrosis factor alpha were reached after 4 h and 2 h , respectively . . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
IFNbeta markedly upregulated CXCR 3 ligand chemokines ( SCYB 11 , SCYB 10 and SCYB 9 ) chiefly active on effector T helper type 1 ( Th 1 ) T cells , and CCR 2 ligand chemokines ( SCYA 8 and SCYA 2 ) effective on monocytes , whereas it downregulated CXCR 2 ligand chemokines ( SCYB 2 , SCYB 1 and IL 8 ) primarily active on neutrophils . ^^^
Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
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Interacting proteins: P13500 and P41597 Pubmed SVM Score :0.0
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