C5b-9 inhibits myelin gene expression in oligodendrocyte progenitor cells (134.68)

Abstract

Abstract Active demyelinating multiple sclerosis (MS) lesions can be subdivided into four neuropathological patterns, based on the presence of immunoglobulins and C5b-9 or evidence of primary oligodendrocyte pathology. Following inflammatory demyelination only partial remyelination occurs and is mediated by oligodendrocyte precursor cells (OPCs). No systematic studies were performed to localize the OPCs in relation to the C5b-9 deposits in MS brains. OPCs we identified by immunohistochemistry using antibodies against NG2, an integral membrane chondroitin sulfate proteoglycan. In addition we examined the deposition of C5b-9 and the presence of inflammatory cells. We detected NG2+ cells in both perivascular and parenchymal areas of MS plaques and normal adjacent white and gray matter areas. A subpopulation of NG2-positive cells also presented C5b-9 deposits and suggests that the terminal complement complex might be involved in OPCs differentiation. To test this hypothesis we investigated in vitro the effect of sublytic C5b-9 on OPC differentiation and expression of myelin genes. Sublytic C5b-9 significantly reduced the accumulation of mRNA encoding proteolipid protein and myelin basic protein. These data are the first to implicate the C5b-9 in the limited remyelination seen in MS lesions. Thus, C5b-9 assembly may represent a potential target for therapeutic intervention in MS.