Release of leukotriene B4 from sublethally injured oligodendrocytes by terminal complement complexes.
In the present study, the interaction of the terminal complement complexes with oligodendrocytes was investigated for observation of its effect on membrane lipid hydrolysis. [14C]Arachidonic acid was incorporated into the membrane lipids of cultured oligodendrocytes before sensitization with anti-galactocerebroside antiserum. Cells were then exposed to excess C6-deficient rabbit serum reconstituted with limiting doses of C6 to form various numbers of C5b-9 complexes. Qualitative analysis of the supernatants by HPLC revealed the presence of compounds that coeluted with arachidonic acid and its oxygenated derivatives, prostaglandin E2, leukotrienes E4 and B4, and 15-hydroxyeicosatetraenoic acid. The kinetics of leukotriene B4 release by excess C5b-8 was quantitated by radioimmunoassay. Leukotriene B4 release approached a maximum around 30 min, and C6 dose-response studies performed at 1 h showed that maximal levels of leukotriene B4 were detected over a range of sublytic C5b-9 attack. Maximal release of leukotriene B4 was also achieved by C5b-8 without further enhancement by addition of lytic doses of C9. Results indicate that sublytic attack of oligodendrocytes by complement induces release of lipid-derived inflammatory mediators.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival; D003182:Complement C5 / Q000276:immunology; D050776:Complement C5b; D003183:Complement C6 / Q000276:immunology; D003186:Complement C9 / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D007700:Kinetics; D007975:Leukotriene B4 / Q000276:immunology*; D008563:Membrane Lipids / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology* / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D003182:Complement C5; D003183:Complement C6; D003186:Complement C9; D008563:Membrane Lipids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D050776:Complement C5b; D003165:Complement System Proteins