MCP-1-dependent signaling in CCR2-/- aortic smooth muscle cells

Alison D. Schecter, Adriane B. Berman, Lin Yi, Harry Ma, Christine M. Daly, Kenzo Soejima, Barrett J. Rollins, Israel F. Charo, Mark B. Taubman

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1079-1085
Number of pages7
JournalJournal of Leukocyte Biology
Volume75
Issue number6
DOIs
Publication statusPublished - 2004 Jun 1
Externally publishedYes

Keywords

  • Chemokine
  • Genetically altered mice
  • Kinases
  • Receptors
  • Tissue factor
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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  • Cite this

    Schecter, A. D., Berman, A. B., Yi, L., Ma, H., Daly, C. M., Soejima, K., Rollins, B. J., Charo, I. F., & Taubman, M. B. (2004). MCP-1-dependent signaling in CCR2-/- aortic smooth muscle cells. Journal of Leukocyte Biology, 75(6), 1079-1085. https://doi.org/10.1189/jlb.0903421