Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions

The pathology of multiple sclerosis (MS) is characterized by breakdown of t he blood-brain barrier (BBB), accompanied by infiltration of macrophages an d T lymphocytes into the central nervous system (CNS), The migration of the se cells into the CNS parenchyma may be partly regulated by chemokines. The aim of this study was therefore to investigate the cellular localization o f the potent monocyte- and T-cell-attracting chemokine monocyte chemoattrac tant protein (MCP)-1 by immunohistochemistry on postmortem brain tissue fro m MS and normal control cases. Brain tissue samples of six MS patients and four patients without a history of brain disease were neuropathologically c lassified according to characteristic (immuno)histochemical staining patter ns. Frozen tissue sections of active demyelinating MS lesions, chronic acti ve demyelinating MS lesions, and normal control brain mere immunohistochemi cally stained with a monoclonal antibody directed against MCP-1. In active demyelinating MS lesions as web as in chronic active MS lesions, reactive h ypertrophic astrocytes were strongly immunoreactive for MCP-1, whereas peri vascular and parenchymal foamy macrophages did not express MCP-1 protein. T hese results suggest a significant role for the beta-chemokine MCP-1, synth esized in vivo by reactive hypertrophic astrocytes, in the recruitment and activation of myelin-degrading macrophages and thereby contributing to the evolution of MS lesions.