MCP-1 receptor binding affinity is up-regulated by pre-stimulation with MCP-1 in an actin polymerization-dependent manner.
Monocyte chemoattractant protein-1 (MCP-1) induces monocyte chemotaxis via interaction with the MCP-1 receptor CCR2. We found that MCP-1 binding to monocytic THP-1 cells was increased by pre-treatment with MCP-1. The amount of CCR2 mRNA and the cell-surface expression of CCR2 were not affected by MCP-1 stimuli. In contrast, the MCP-1-treated THP-1 cells showed a sixfold increase in MCP-1 binding affinity compared with untreated cells. MCP-1 binding to CCR2B-transfected HEK-293 cells was also enhanced by pre-treatment with MCP-1, and MCP-1 binding affinity increased by sixfold. In both cell lines, the enhancement of MCP-1 binding by stimulation with MCP-1 was blocked by cytochalasin D, an inhibitor of actin polymerization. This effect of pre-treatment with MCP-1 is insensitive to pertussis toxin and partially blocked by U73122, an inhibitor of phospholipase C. These results demonstrate that the MCP-1 receptor binding affinity is up-regulated by MCP-1 stimuli in an actin polymerization-dependent manner.
Kito
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New Product Research Laboratories II, Daiichi Pharmaceutical Company Ltd., Tokyo, Japan. kitok7m2@daiichipharm.co.jp
Morishita
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Nishida
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D000199:Actins / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D001704:Biopolymers; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
D000199:Actins; D000730:Androstadienes; D001704:Biopolymers; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D004963:Estrenes; D046911:Macromolecular Substances; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D003571:Cytochalasin B; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D019311:Staurosporine; D000077191:Wortmannin