Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice.
Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, but the signals that initiate their recruitment to the vessel wall are poorly understood. Here, we review in vivo studies in genetically altered mice that support the notion that monocyte chemoattractant protein-1 (a member of the chemokine family of chemotactic cytokines) and chemokine receptor 2 (its cognate receptor) play important roles in this recruitment. An unexpected finding in chemokine receptor 2-knockout mice was the diminished production of interferon-gamma, which is a potent macrophage activator. The basis of this cytokine defect is not yet clear, but suggests that chemokines may influence atherosclerotic lesion development at several levels. Understanding the roles of chemokines and cytokines in atherogenesis may provide a basis for the development of future therapeutic agents that are aimed at interrupting monocyte recruitment and activation.
Peters
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Gladstone Institute of Cardiovascular Disease, and Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, California 94141-9100, USA.
Charo
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D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology; D018932:Chemokine CCL2 / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D007371:Interferon-gamma