title: Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59.
abstract: 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.
authors.affiliation: Molecular Immunopathology Unit, Addenbrookes Hospital, Cambridge, U.K.
authors.forename: M G
authors.initials: MG
authors.lastname: Wing
authors.forename: J
authors.initials: J
authors.lastname: Zajicek
authors.forename: D J
authors.initials: DJ
authors.lastname: Seilly
authors.forename: D A
authors.initials: DA
authors.lastname: Compston
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
mesh_terms: 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
chemical_list: 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