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MCP‐1‐dependent signaling in CCR2 −/− aortic smooth muscle cells
Author(s) -
Schecter Alison D.,
Berman Adriane B.,
Yi Lin,
Ma Harry,
Daly Christine M.,
Soejima Kenzo,
Rollins Barrett J.,
Charo Israel F.,
Taubman Mark B.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0903421
Subject(s) - ccr2 , pertussis toxin , biology , microbiology and biotechnology , signal transduction , receptor , heterotrimeric g protein , monocyte , p38 mitogen activated protein kinases , chemotaxis , inflammation , g protein , g protein coupled receptor , mapk/erk pathway , chemokine , chemokine receptor , biochemistry , immunology
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 G αi ‐coupled and dependent on mobilization of intracellular Ca 2+ . 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.