Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59.
Rat oligodendrocytes, which activate the classical pathway of complement in the absence of antibody, are highly sensitive in a reactive lysis assay using human C5b6 and EDTA serum. Oligodendrocytes may be relatively deficient in glycolipid-linked complement regulatory protein(s), since digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) failed to increase their sensitivity to serum, whereas complement-insensitive astrocytes, when treated with PI-PLC, became strikingly sensitive. To test the hypothesis that oligodendrocytes lack terminal complement regulatory molecule(s), human erythrocyte CD59, a recently described complement regulatory protein, was purified to homogeneity. The biological activity of the preparation was confirmed by reincorporating the protein into guinea-pig erythrocytes through its glycolipid anchor, which resulted in dose-dependent protection against human C5b6 and EDTA serum. Incorporation of 10(5) molecules of human CD59 into rat oligodendrocytes resulted in good protection against homologous human complement (76%), and significant protection against rat complement homologous to the cell (36%). Protection could be reversed using an antibody to CD59.
Wing
M G
MG
Molecular Immunopathology Unit, Addenbrookes Hospital, Cambridge, U.K.
Zajicek
J
J
Seilly
D J
DJ
Compston
D A
DA
Lachmann
P J
PJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018957:CD59 Antigens; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006017:Glycolipids / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D015703:Antigens, CD; D018957:CD59 Antigens; D006017:Glycolipids; D008562:Membrane Glycoproteins; D003165:Complement System Proteins; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase