Wu R, Huang Y H, Elinder L S, Frostegård J
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 1998 Apr;18(4):626-30. doi: 10.1161/01.atv.18.4.626.
Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density lipoprotein (LDL) and cell membranes by phospholipase A2 or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclerosis. The antigen in oxLDL responsible for its immune-stimulatory capacity is not well characterized, and we hypothesized that LPC was involved. 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 acid moiety in LPC, since LPC containing only palmitic acid showed antibody titers equivalent to those of LPC containing unsaturated fatty acids. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity. There was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity, which indicates that LPC may explain a significant part of the immune-stimulatory properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself. Instead, LPC could form immunogenic complexes with peptides, which may induce and potentiate immune reactions in the vessel wall. This study adds to the evidence that LPC is an important component of oxLDL and emphasizes the potential role of phospholipase A2 in atherosclerosis.
溶血磷脂酰胆碱(LPC)是由磷脂酶A2或氧化作用使低密度脂蛋白(LDL)和细胞膜中的磷脂酰胆碱(PC)水解形成的。氧化型(ox)LDL可激活内皮细胞,LPC也有类似作用。oxLDL还具有激活T细胞和B细胞的能力,针对oxLDL的抗体滴度与动脉粥样硬化程度相关。oxLDL中具有免疫刺激能力的抗原尚未完全明确,我们推测LPC与之有关。我们在此证明,在210名健康个体中存在IgG和IgM同种型的抗LPC抗体。这种抗体反应性与LPC中脂肪酸部分的氧化并无特异性关联,因为仅含棕榈酸的LPC显示出与含不饱和脂肪酸的LPC相当的抗体滴度。与LPC相比,针对PC的抗体滴度较低,因此PC在sn-2位的水解对于免疫反应性至关重要。抗oxLDL抗体与抗LPC抗体之间存在密切相关性。此外,LPC竞争性抑制抗oxLDL反应性,这表明LPC可能在很大程度上解释了oxLDL的免疫刺激特性。LPC作为一种脂质,本身不太可能是抗原。相反,LPC可能与肽形成免疫原性复合物,从而在血管壁中诱导并增强免疫反应。这项研究进一步证明LPC是oxLDL的重要组成部分,并强调了磷脂酶A2在动脉粥样硬化中的潜在作用。