Jerome W G, Cash C, Webber R, Horton R, Yancey P G
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1092, USA.
J Lipid Res. 1998 Jul;39(7):1362-71.
Lipid accumulation within macrophages is a major sequelae of atherosclerosis. Much of this lipid accumulation occurs within large, swollen lysosomes. We analyzed lipid accumulation in cultured macrophages using oxidized or acetylated low density lipoprotein (LDL) as the loading agent. Pigeon macrophages incubated for 48 h with mildly oxidized pigeon LDL (TBARS = 5-10 nmol/mg protein) showed significant increases in cellular cholesterol compared with untreated controls. Forty-eight percent of the increased cholesterol occurred as unesterified cholesterol. Treated cells had lipid-swollen lysosomes similar to those of atherosclerotic foam cells. The increase in lysosomal lipid was accompanied (correlation coefficient of 0.96) by increases in acid phosphatase staining cisternae of the Golgi and trans-Golgi network (TGN). THP-1 macrophages incubated with oxidized LDL showed similar lysosomal loading and Golgi/TGN hypertrophy. In contrast, macrophages incubated with acetylated LDL accumulated significant amounts of cholesterol but the increase occurred as cholesteryl ester (81% in pigeons) within cytoplasmic droplets and there was no associated increase in acid phosphatase-containing cisternae of Golgi or TGN. The correlation in both pigeon and THP-1 macrophages of oxidized LDL-induced lysosomal lipid accumulation and Golgi hypertrophy suggests a linkage of these two phenomena. This implicates intracellular membrane trafficking as a possible defect in foam cells of the atherosclerotic lesion.
巨噬细胞内的脂质积累是动脉粥样硬化的主要后遗症。这种脂质积累大多发生在大的、肿胀的溶酶体内。我们使用氧化型或乙酰化型低密度脂蛋白（LDL）作为加载剂，分析了培养的巨噬细胞中的脂质积累情况。用轻度氧化的鸽LDL（硫代巴比妥酸反应物 = 5 - 10 nmol/mg蛋白质）孵育48小时的鸽巨噬细胞，与未处理的对照相比，细胞胆固醇显著增加。增加的胆固醇中有48%以未酯化胆固醇的形式存在。处理过的细胞有类似于动脉粥样硬化泡沫细胞的脂质肿胀溶酶体。溶酶体脂质的增加伴随着高尔基体和反式高尔基体网络（TGN）酸性磷酸酶染色池的增加（相关系数为0.96）。用氧化型LDL孵育的THP - 1巨噬细胞显示出类似的溶酶体加载和高尔基体/TGN肥大。相比之下，用乙酰化LDL孵育的巨噬细胞积累了大量胆固醇，但增加的是以胆固醇酯的形式（鸽中为81%）存在于细胞质液滴中，并且高尔基体或TGN中含酸性磷酸酶的池没有相关增加。氧化型LDL诱导的鸽和THP - 1巨噬细胞溶酶体脂质积累与高尔基体肥大之间的相关性表明这两种现象存在联系。这意味着细胞内膜运输可能是动脉粥样硬化病变泡沫细胞中的一个缺陷。
