MCP-1-dependent signaling in CCR2(-/-) aortic smooth muscle cells
| Autor: | Israel F. Charo, Mark B. Taubman, Lin Yi, Adriane B. Berman, Barrett J. Rollins, Harry Ma, Christine M. Daly, Kenzo Soejima, Alison D. Schecter |
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| Rok vydání: | 2004 |
| Předmět: |
CCR2
Vascular smooth muscle Receptors CCR2 p38 mitogen-activated protein kinases Immunology Biology GTP-Binding Protein alpha Subunits Gi-Go Pertussis toxin p38 Mitogen-Activated Protein Kinases Monocytes Muscle Smooth Vascular Thromboplastin Tissue factor Mice Heterotrimeric G protein Immunology and Allergy Animals Enzyme Inhibitors Phosphorylation Receptor Aorta Cells Cultured Chemokine CCL2 Mice Knockout Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Homozygote Cell Biology Recombinant Proteins Cell biology Pertussis Toxin Calcium Receptors Chemokine Signal transduction Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | Journal of leukocyte biology. 75(6) |
| ISSN: | 0741-5400 |
| Popis: | Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a mediator of inflammation that has been implicated in the pathogenesis of a wide variety of human diseases. CCR2, a heterotrimeric G-coupled receptor, is the only known receptor that functions at physiologic concentrations of MCP-1. Despite the importance of CCR2 in mediating MCP-1 responses, several recent studies have suggested that there may be another functional MCP-1 receptor. Using arterial smooth muscle cells (SMC) from CCR2−/− mice, we demonstrate that MCP-1 induces tissue-factor activity at physiologic concentrations. The induction of tissue factor by MCP-1 is blocked by pertussis toxin and 1,2-bis(O-aminophenyl-ethane-ethan)-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester, suggesting that signal transduction through the alternative receptor is Gαi-coupled and dependent on mobilization of intracellular Ca2+. MCP-1 induces a time- and concentration-dependent phosphorylation of the mitogen-activated protein kinases p42/44. The induction of tissue factor activity by MCP-1 is blocked by PD98059, an inhibitor of p42/44 activation, but not by SB203580, a selective p38 inhibitor. These data establish that SMC possess an alternative MCP-1 receptor that signals at concentrations of MCP-1 that are similar to those that activate CCR2. This alternative receptor may be important in mediating some of the effects of MCP-1 in atherosclerotic arteries and in other inflammatory processes. |
| Databáze: | OpenAIRE |
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