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Monocyte Chemoattractant Protein‐1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and Controversies
Author(s) -
DALY CHRISTINE,
ROLLINS BARRETT J.
Publication year - 2003
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1038/sj.mn.7800190
Subject(s) - ccr2 , ccl2 , monocyte , immunology , chemokine , acquired immune system , chemotaxis , phenotype , biology , ccl3 , immune system , receptor , chemokine receptor , gene , genetics
Monocyte chemoattractant protein (MCP)‐1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small‐molecule antagonists of the receptor of MCP‐1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP‐1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP‐1/CCL2 −/− and CCR2 −/− mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP‐1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP‐1/CCL2/CCR2 axis in disease.