Lipton B A, Parthasarathy S, Ord V A, Clinton S K, Libby P, Rosenfeld M E
Department of Medicine, University of California San Diego, La Jolla, USA.
J Lipid Res. 1995 Oct;36(10):2232-42.
Oxidized low density lipoproteins (oxLDL) (0.5-50 micrograms/ml) generated from both rabbit and human LDL stimulated the production of interleukin-1 alpha (IL-1 alpha) by as much as 2- and 6-fold, respectively, as compared to native LDL after a 2-h incubation with macrophage-derived foam cells isolated from the balloon-injured arteries of cholesterol-fed rabbits. Northern blot analyses confirmed that there was also an increase in the mRNA for IL-1 alpha and IL-beta in response to oxLDL in the isolated foam cells. The stimulation of IL-1 expression and production was not due to the contamination of the oxLDL preparations with endotoxin as neither the amount of endotoxin found to be associated with the lipoproteins nor amounts up to 1 ng/ml stimulated IL-1 alpha production to the same degree as oxLDL. Neither oxidized beta-very low density lipoprotein (VLDL) nor oxidized high density lipoprotein (HDL) stimulated IL-1 alpha production by the foam cells. Furthermore, acetyl-LDL had a very limited stimulatory effect, but other known ligands of the scavenger receptor such as maleylated-BSA, polyinosinic acid, and fucoidin elicited maximal IL-1 alpha responses. Fractionation of the oxLDL into lipid- and protein-soluble fractions showed that there was some stimulatory activity in the lipid phase but that known products of lipid peroxidation such as 9- and 13-HODE had no effect when added independently of lipoproteins. When added in combination with native LDL, only 13-HODE stimulated IL-1 alpha production. The delipidated apolipoprotein fragments of oxLDL that had been solubilized in beta-octylglucoside stimulated the production of IL-1 alpha by the foam cells to a greater degree than the lipid extract, while reductively methylated oxLDL did not. These data suggest that interactions of components of both the lipid- and protein-soluble fractions of oxLDL with scavenger receptors or potentially with surface proteins that bind oxLDL may induce production of IL-1 by arterial macrophages.
与天然低密度脂蛋白（LDL）相比，来自兔和人LDL产生的氧化型低密度脂蛋白（oxLDL）（0.5 - 50微克/毫升）分别与从高胆固醇喂养兔的球囊损伤动脉分离的巨噬细胞源性泡沫细胞孵育2小时后，刺激白细胞介素-1α（IL-1α）的产生高达2倍和6倍。Northern印迹分析证实，分离的泡沫细胞中，响应oxLDL时，IL-1α和IL-β的mRNA也增加。IL-1表达和产生的刺激并非由于oxLDL制剂被内毒素污染，因为与脂蛋白相关的内毒素量以及高达1纳克/毫升的量均未像oxLDL那样刺激IL-1α产生。氧化型β-极低密度脂蛋白（VLDL）和氧化型高密度脂蛋白（HDL）均未刺激泡沫细胞产生IL-1α。此外，乙酰化LDL具有非常有限的刺激作用，但清道夫受体的其他已知配体，如马来酰化牛血清白蛋白、聚肌苷酸和岩藻依聚糖引发最大的IL-1α反应。将oxLDL分离为脂质和蛋白质可溶部分表明，脂质相中存在一些刺激活性，但脂质过氧化的已知产物，如9-和13-羟基十八碳二烯酸（HODE）在独立于脂蛋白添加时没有作用。当与天然LDL联合添加时，只有13-HODE刺激IL-1α产生。已溶解在β-辛基葡糖苷中的oxLDL的脱脂载脂蛋白片段比脂质提取物更能刺激泡沫细胞产生IL-1α，而还原甲基化的oxLDL则不能。这些数据表明，oxLDL的脂质和蛋白质可溶部分的成分与清道夫受体或可能与结合oxLDL的表面蛋白之间的相互作用可能诱导动脉巨噬细胞产生IL-1。
