Glial CellsNeuronal protection of oligodendrocytes from antibody-independent complement lysisAgoropoulou, C1; Piddlesden, S J.2; Lachmann, P J.1; Wing, M G.1,3,4Author Information 1MRC Molecular Immunopathology Unit, Hills Road, Cambridge, CB2 2QH 2Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, CF4 4XN 3University of Cambridge Neurology unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK 4Corresponding Author: M. G. Wing ACKNOWLEDGEMENTS: This work was supported by the Multiple Sclerosis Society of Great Britain and Northern Ireland. Received 26 November 1997; accepted 13 January 1998 NeuroReport: March 30th, 1998 - Volume 9 - Issue 5 - p 927-932 Buy Abstract CULTURED rat oligodendrocytes are lysed by complement via antibody—independent activation of the classical pathway. This susceptibility to complement lysis has been demonstrated to be due to lack of CD59, a complement regulatory protein which inhibits assembly of the membrane attack complex. In this study the effects of homologous and heterologous complement were examined in a co-culture system of rat oligodendrocytes and peripheral neurones, where axonal ensheathment was observed as early 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-dependent complement lysis than were cells grown without neurones. Immunocytochemical data revealed that co-cultured oligodendrocytes remained CD59 negative, but in contrast to oligodendrocytes cultured alone, were negative for C3b when incubated with C7-deficient serum. Taken together these data indicate that the decreased sensitivity of co-cultured oligodendrocytes to complement lysis is not attributed to the increased expression of CD59, but rather in a failure to activate complement. Incubation of oligodendrocytes with neurone-conditioned medium afforded significant protection (68%), against antibody—independent complement attack, suggesting that soluble neuronal factors can protect oligodendrocytes from complement-mediated lysis. © Lippincott-Raven Publishers.