NEURONAL PROTECTION OF OLIGODENDROCYTES FROM ANTIBODY-INDEPENDENT COMPLEMENT LYSIS

CULTURED rat oligodendrocytes are lysed by complement via antibody-ind ependent activation of the classical pathway. This susceptibility to c omplement lysis has been demonstrated to be due to lack of CD59, a com plement regulatory protein which inhibits assembly of the membrane att ack complex. In this study the effects of homologous and heterologous complement were examined in a co-culture system of rat oligodendrocyte s and peripheral neurones, where axonal ensheathment was observed as e arly as 4 days after the addition of glial progenitors to the neurones . Following exposure to complement, ensheathing oligodendrocytes were markedly less sensitive to antibody-independent but not antibody-depen dent complement lysis than were cells grown without neurones. Immunocy tochemical data revealed that co-cultured oligodendrocytes remained CD 59 negative, but in contrast to oligodendrocytes cultured alone, were negative for C3b when incubated with C7-deficient serum. Taken togethe r these data indicate that the decreased sensitivity of co-cultured ol igodendrocytes to complement lysis is not attributed to the increased expression of CD59, but rather in a failure to activate complement. In cubation of oligodendrocytes with neurone-conditioned medium afforded significant protection (68%), against antibody-independent complement attack, suggesting that soluble neuronal factors can protect oligodend rocytes from complement-mediated lysis. (C) 1998 Rapid Science Ltd.