HUMAN MONOCYTE CHEMOTACTIC PROTEIN-2 AND PROTEIN-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, MCP s are produced by a variety of cells on stimulation with cytokines (in terleukin-1, tumor necrosis factor-alpha, interferon-gamma), bacterial and viral products or mitogens, MCP-1 levels are enhanced during infe ction and inflammation, which are characterized by leukocyte infiltrat ion, In vitro, MCPs are chemotactic for a distinct spectrum of target cells and show different specific biological activities depending on t he cell type and the chemokine tested, MCP-3 has the broadest range in that it activates monocytes, dendritic cells, lymphocytes, natural ki ller cells, eosinophils, basophils, and neutrophils, The most sensitiv e cells to all three MCPs are lymphocytes and monocytes, MCP-1 is a po tent basophil activator but does not attract eosinophils, whereas, at higher concentrations, MCP-2 also stimulates both eosinophils and baso phils, 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 an d C-C CKR-2 binds MCP-1 and MCP-S but not MCP-2. Receptor binding lead s to enhanced [Ca2+](i) for all chemokines except for MCP-2.