title: Neuronal protection of oligodendrocytes from antibody-independent complement lysis.
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.
authors.affiliation: MRC Molecular Immunopathology Unit, Cambridge, UK.
authors.forename: C
authors.initials: C
authors.lastname: Agoropoulou
authors.forename: S J
authors.initials: SJ
authors.lastname: Piddlesden
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: M G
authors.initials: MG
authors.lastname: Wing
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018957:CD59 Antigens / Q000096:biosynthesis; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D017077:Culture Media, Conditioned; D005727:Ganglia, Spinal / Q000166:cytology; D006461:Hemolysis; D018613:Microscopy, Confocal; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology
chemical_list: D018957:CD59 Antigens; D017077:Culture Media, Conditioned; D004676:Myelin Basic Protein; D003165:Complement System Proteins