Anti-liposome antibodies induced by lipid A. I. Influence of ceramide, glycosphingolipids, and phosphocholine on complement damage.

Abstract

Abstract Anti-liposome (anti-phosphatidylcholine) antibodies were produced in rabbits either by injection of phosphatidylcholine liposomes containing lipid A or, in the absence of phosphatidylcholine, by injection of acid-treated bacterial cells coated with lipid A. Complement- (C) dependent membrane damage mediated by anti-liposome antibodies was markedly enhanced by inclusion of glycosyl ceramide, or ceramide alone, in the liposomes. Adsorption studies demonstrated that, with the antiserum tested, liposomes containing ceramide absorbed fewer antibodies than did liposomes lacking ceramide, and therefore enhancement by ceramide was due to increased C activation, rather than due to increased binding of anti-liposome antibodies. None of the enhancing effect of glycosyl ceramide was due to presence of anti-glycosyl ceramide antibodies in the antiserum. Bona fide anti-galactosyl ceramide antibodies did not react significantly with liposomes lacking glycolipid, or with liposomes containing ceramide, glucosyl ceramide, or lipid A. Incubation of liposomes containing membrane glycolipid with soluble phosphocholine caused either inhibition or stimulation of anti-phosphatidylcholine antibody activity, depending on the antiserum used, liposome composition, and phosphocholine concentration. Phosphocholine could be bound to liposomes under certain conditions, and resultant agglutination of liposomes was observed. Increased immune damage in the presence of phosphocholine, when it occurred, was due to binding of phosphocholine to the liposomes, resulting in increased antigen concentration at the membrane surface. We conclude that: a) even in the absence of liposomes, or in the absence of injected phosphatidylcholine or sphingomyelin, lipid A can induce anti-liposome (mainly anti-phosphatidylcholine) antibodies; b) a glycosphingolipid, or even ceramide alone, can enhance C damage mediated by antibodies against certain lipid antigens in lipid membranes; and c) phosphocholine can bind non-specifically to liposomes and cause further binding of anti-liposome (anti-phosphocholine) antibodies.