Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1.
Structurally, the monocyte chemotactic proteins MCP-1, -2, and -3 form a subfamily of the C-C or beta-chemokines. Like other chemokines, MCPs are produced by a variety of cells on stimulation with cytokines (interleukin-1, tumor necrosis factor-alpha, interferon-gamma), bacterial and viral products or mitogens. MCP-1 levels are enhanced during infection and inflammation, which are characterized by leukocyte infiltration. In vitro, MCPs are chemotactic for a distinct spectrum of target cells and show different specific biological activities depending on the cell type and the chemokine tested. MCP-3 has the broadest range in that it activates monocytes, dendritic cells, lymphocytes, natural killer cells, eosinophils, basophils, and neutrophils. The most sensitive cells to all three MCPs are lymphocytes and monocytes. MCP-1 is a potent basophil activator but does not attract eosinophils, whereas, at higher concentrations, MCP-2 also stimulates both eosinophils and basophils. The signal transduction of MCPs on monocytes involves at least two G protein-linked C-C chemokine receptors: C-C CKR-1 binds MCP-3 and C-C CKR-2 binds MCP-1 and MCP-3 but not MCP-2. Receptor binding leads to enhanced [Ca2+]i for all chemokines except for MCP-2.
Proost
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P
Rega Institute for Medical Research, University of Leuven, Belgium.
Wuyts
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A
Van Damme
J
J
D000595:Amino Acid Sequence; D018932:Chemokine CCL2 / Q000737:chemistry / Q000502:physiology; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000737:chemistry* / Q000502:physiology*; D016207:Cytokines; D006801:Humans; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000737:chemistry / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
C515450:CCL7 protein, human; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins