Production and function of monocyte chemoattractant protein-1 and other β-chemokines in murine glial cells

Abstract

Monocyte chemoattractant protein-1 (MCP-1), formerly termed JE, is a member of the β-chemokine (CC 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 allergic 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 cells has not been fully examined. Using a sandwich ELISA assay, we have now quantitated MCP-1 levels and assessed MCP-1 function on murine glial cells. Lipopolysaccharide (LPS), interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced MCP-1 secretion by astrocytes, but not microglia. In addition, pretreatment with interferon (IFN)-y significantly augmented MCP-1 production by either LPS or the above cytokines. In contrast, LPS preferentially induced production of another β-chemokine, macrophage inflammatory protein-1α (MIP-1α) from microglial cells. MCP-1 induced chemotaxis of microglial cells and macrophages. Similarly, another β-chemokine, TCA3, which is produced by encephalitogenic T lymphocytes, also induced chemotaxis of microglia and macrophages. These findings suggested that astrocytes and microglial cells differentially produce chemokines in the central nervous system, and that both astrocytes and T cells may facilitate recruitment and activation of microglial cells via production of β -chemokines. © 1995.