Effect of erythrocyte membrane modulation by lysolecithin on complement-mediated lysis.
Alterations of the physiochemical properties of membranes, such as acyl chain length of phospholipids, cholesterol content, and disturbance of the bilayer packing, affect the efficiency of membrane attack by C5b-9. In the present study, we explored the effect of lysolecithin (LL), a naturally occurring derivative of membrane phospholipids, on membrane damage by C5b-9. Sublytic doses of the L isomer of palmitoyl-lysolecithin were incorporated into the erythrocyte membranes of guinea pig (gpE) or sheep (shE) and the cells were then lysed with C5b6-C9. Marked enhancement of complement-mediated lysis was observed with LL-treated gpE after 2 hr of incubation, whereas the lytic enhancement was either nil or only marginal in shE. Studies on the kinetics of LL incorporation and metabolism in gpE membranes with 14C-LL showed that LL was rapidly incorporated and catabolized to generate free fatty acid (FA). Maximal accumulation of labeled FA in the membrane and loss of membrane-incorporated LL, resulting in approximately equimolar amounts of LL and FA, occurred at 2 hr, concomitant with enhancement of complement-mediated lysis. In shE such a breakdown of LL occurred only minimally. This quantitative difference in LL breakdown between gpE and shE was in accord with lysophospholipase activity that was two and one-half to seven times more active in gpE than shE membranes. When an ether-linked analog of LL (1-O-hexadecyl-sn-phosphorylcholine), which is resistant to lysophospholipase, was incorporated in gpE, the lytic enhancement was not observed. The results of our experiments indicate that the membrane modulating effect of LL on lysis by C5b-9 requires the enzymatic breakdown of LL.
D000818:Animals; D003167:Complement Activation; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008245:Lysophospholipase / Q000097:blood; D008563:Membrane Lipids / Q000097:blood; D012756:Sheep
D015938:Complement Membrane Attack Complex; D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; C006065:We 201; D003165:Complement System Proteins; D008245:Lysophospholipase