PRODUCTION AND FUNCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND OTHER BETA-CHEMOKINES IN MURINE GLIAL-CELLS

Monocyte chemoattractant protein-1 (MCP-1), formerly termed JE, is a m ember of the beta-chemokine (C-C chemokine) family and has been shown to be produced by a variety of cell types. Recently, mRNA of JE/MCP-1 was detected in astrocytes during the acute phase of experimental alle rgic encephalomyelitis (EAE). In addition, supernatants collected from human cultured astrocytes have recently been found to be chemotactic for monocytes. However, chemokine production and function in glial cel ls has not been fully examined. Using a sandwich ELISA assay, we have now quantitated MCP-I levels and assessed MCP-1 function on murine gli al cells. Lipopolysaccharide (LPS), interleukin (IL)-1 beta and tumor necrosis factor(TNF)-alpha induced MCP-1 secretion by astrocytes, but not microglia. In addition, pretreatment with interferon (IFN)-gamma s ignificantly augmented MCP-1 production by either LPS or the above cyt okines. In contrast, LPS preferentially induced production of another beta-chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha) from microglial cells. MCP-1 induced chemotaxis of microglial cells an d macrophages. Similarly, another beta-chemokine, TCA3, which is produ ced by encephalitogenic T lymphocytes, also induced chemotaxis of micr oglia and macrophages. These findings suggested that astrocytes and mi croglial cells differentially produce chemokines in the central nervou s system, and that both astrocytes and T cells may facilitate recruitm ent and activation of microglial cells via production of beta-chemokin es.