LYSOPHOSPHATIDYLCHOLINE IS INVOLVED IN THE ANTIGENICITY OF OXIDIZED LDL

Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low den sity lipoprotein (LDL) and cell membranes by phospholipase A(2) or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mi micked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclero sis. The antigen in oxLDL responsible for its immune-stimulatory capac ity is not well characterized, and we hypothesized that LPC was involv ed. We demonstrate herein the presence of antibodies against LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody reactivity was not specifically related to oxidation of the fatty aci d moiety in LPC, since LPC containing only palmitic acid showed antibo dy titers equivalent to those of LPC containing unsaturated fatty acid s. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity, Ther e was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity which i ndicates that LPC may explain a significant part of the immune-stimula tory properties of oxLDL. LPC, being a lipid, is not likely to be an a ntigen itself. Instead, LPC could form immunogenic complexes with pept ides, which may induce and potentiate immune reactions in the vessel w all. This study adds to the evidence that LPC is an important componen t of oxLDL and emphasizes the potential role of phospholipase A(2) in atherosclerosis.