EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND OTHER BETA-CHEMOKINES BY RESIDENT GLIA AND INFLAMMATORY CELLS IN MULTIPLE-SCLEROSIS LESIONS

beta-chemokines induce the directional migration of monocytes and T ly mphocytes and are thus associated with chronic inflammation. Using imm unocytochemistry and in situ hybridisation (ISH) techniques, we have e xamined the expression of the beta-chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha, MIP -1 beta, and RANTES (regulated upon activation, normal T cell expresse d and secreted) in post-mortem human brain from multiple sclerosis (MS ) cases? at different stages of lesion development. In actively demyel inating MS plaques RANTES expression was restricted to the blood vesse l endothelium, perivascular cells and surrounding astrocytes, suggesti ng a role in the recruitment of inflammatory cells from the circulatio n. MCP-I was expressed by astrocytes and macrophages within acute RIS lesions, but was restricted to reactive astrocytes in the parenchyma s urrounding the lesion. MIP-1 alpha was expressed by astrocytes and mac rophages within the plaque, while MIP-1 beta was expressed by macropha ges and microglia within the lesion, and by microglia in surrounding w hite matter. Glial cells may be stimulated to produce chemokines and c ontinue the local inflammatory response by forming chemotactic gradien ts to attract T cells and mononuclear phagocytes from the circulation and surrounding tissue. (C) 1998 Elsevier Science B.V.