Neuronal protection of oligodendrocytes from antibody-independent complement lysis.
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.
Agoropoulou
C
C
MRC Molecular Immunopathology Unit, Cambridge, UK.
Piddlesden
S J
SJ
Lachmann
P J
PJ
Wing
M G
MG
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
D018957:CD59 Antigens; D017077:Culture Media, Conditioned; D004676:Myelin Basic Protein; D003165:Complement System Proteins