ENHANCED MACROPHAGE DEGRADATION OF LOW-DENSITY LIPOPROTEIN PREVIOUSLY INCUBATED WITH CULTURED ENDOTHELIAL-CELLS - RECOGNITION BY RECEPTORS FOR ACETYLATED LOW-DENSITY LIPOPROTEINS
ENHANCED MACROPHAGE DEGRADATION OF LOW-DENSITY LIPOPROTEIN PREVIOUSLY INCUBATED WITH CULTURED ENDOTHELIAL-CELLS - RECOGNITION BY RECEPTORS FOR ACETYLATED LOW-DENSITY LIPOPROTEINS
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DOI：
10.1073/pnas.78.10.6499
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
STEINBERG, D
中科院分区：
文献类型：
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作者：
HENRIKSEN, T;MAHONEY, EM;STEINBERG, D
将人低密度脂蛋白(LDL)与已建立的兔主动脉内皮细胞系孵育。密度梯度分级显示低密度脂蛋白的平均密度随时间、浓度和温度的增加而增加(从约1.036增加到高达1.070克/毫升)。无细胞孵育或与其他类型的培养细胞(成纤维细胞、肝细胞、3T3-L1细胞)孵育后，密度没有明显变化。~(125)I标记的低密度脂蛋白(~(125)I-低密度脂蛋白)与内皮细胞孵育后被内皮细胞(EC-修饰的低密度脂蛋白)摄取并降解的速度是对照低密度脂蛋白的3-4倍。巨噬细胞对EC修饰的125I-LDL的降解呈现饱和动力学(>；85%被过量的未标记EC修饰的低密度脂蛋白抑制)。未标记的乙酰化低密度脂蛋白也抑制了降解，相反，未标记的EC修饰的低密度脂蛋白抑制了乙酰化的125I-低密度脂蛋白的降解。用从内皮细胞培养中取出的条件培养液孵育低密度脂蛋白，既不改变其密度，也不改变其被巨噬细胞降解的速度。内皮细胞具有代谢修饰低密度脂蛋白分子的潜力，产生一种更快被巨噬细胞降解的形式，并被乙酰化低密度脂蛋白的巨噬细胞受体识别。这一过程可能在动脉粥样硬化的发病机制中起重要作用。
Human low density lipoprotein (LDL) was incubated with an established line of rabbit aortic endothelial cells. Density gradient fractionation showed a time-, concentration- and temperature-dependent increase in the average density of the LDL (from about 1.036 to as high as 1.070 g/ml). Incubation without cells or with other types of cultured cells (fibroblasts, hepatocytes, 3T3-L1 cells) caused no significant change in density. 125I-Labeled LDL (125I-LDL) recovered after incubation with endothelial cells (EC-modified LDL) was taken up and degraded 3-4 times more rapidly than control LDL by resident mouse peritoneal macrophages and by an established tumor line of mouse macrophages (J774 cells). Macrophage degradation of EC-modified 125I-LDL exhibited saturation kinetics (> 85% inhibited by excess unlabeled EC-modified LDL). Degradation was also inhibited by unlabeled acetylated LDL and, conversely, unlabeled EC-modified LDL inhibited degradation of acetylated 125I-LDL. Incubation of LDL with conditioned medium removed from endothelial cell cultures modified neither its density nor its rate of degradation by macrophages. Endothelial cells have the potential to metabolically modify the LDL molecule, generating a form that is more rapidly degraded by macrophages and is recognized by the macrophage receptor for acetylated LDL. This process may play a significant role in the pathogenesis of atherosclerosis.