Mahley R W, Innerarity T L, Brown M S, Ho Y K, Goldstein J L
J Lipid Res. 1980 Nov;21(8):970-80.
Animals fed cholesterol accumulate several types of cholesterol-rich lipoproteins in their plasma and ultimately develop cholesteryl ester deposition in tissue macrophages. Previous studies in the cholesterol-fed dog have shown that one class of cholesterol-rich lipoproteins. beta-migrating very low density lipoproteins (beta-VLDL, density < 1.006 g/ml), possesses a unique ability to produce cellular cholesteryl ester accumulation when incubated with mouse peritoneal macrophages in vitro. This accumulation results from the receptor-mediated uptake of beta-VLDL with subsequent lysosomal hydrolysis of the lipoprotein and re-esterification of the liberated cholesterol. In the current studies, we demonstrate that beta-VLDL obtained from cholesterol-fed animals of several other species, including monkeys, rabbits, and rats, also causes cholesteryl ester accumulation in monolayers of mouse peritoneal macrophages, as monitored by an increase in the rate at which the cells incorporate exogenous [14C]oleate into cholesteryl [14C]oleate. Like canine beta-VLDL, the beta-VLDL from these three other species were effective at low concentrations and exhibited saturation kinetics, suggesting that they, too, entered macrophages by receptor-mediated endocytosis. Very low density lipoprotein (VLDL) from normal animals and low density lipoprotein (LDL) from normal and cholesterol-fed monkeys, rats, and rabbits did not stimulate cholesteryl ester synthesis in mouse peritoneal macrophages. In addition to their effects on mouse macrophages, the beta-VLDL from cholesterol-fed dogs and rabbits stimulated cholesteryl ester synthesis in cultured human monocytes. The current findings suggest that beta-VLDL from cholesterol-fed animals has the general property of stimulating cholesteryl ester synthesis and accumulation in macrophages.
喂食胆固醇的动物血浆中会积累几种富含胆固醇的脂蛋白，最终在组织巨噬细胞中形成胆固醇酯沉积。先前对喂食胆固醇的犬类的研究表明，一类富含胆固醇的脂蛋白，即β迁移极低密度脂蛋白（β-VLDL，密度<1.006 g/ml），在体外与小鼠腹腔巨噬细胞孵育时具有产生细胞胆固醇酯积累的独特能力。这种积累是由于β-VLDL通过受体介导的摄取，随后脂蛋白在溶酶体中水解，释放的胆固醇再酯化所致。在当前的研究中，我们证明，从包括猴子、兔子和大鼠在内的其他几种喂食胆固醇的动物中获得的β-VLDL，也会导致小鼠腹腔巨噬细胞单层中的胆固醇酯积累，这可通过细胞将外源性[14C]油酸酯掺入胆固醇[14C]油酸酯的速率增加来监测。与犬类β-VLDL一样，来自其他三个物种的β-VLDL在低浓度下有效，并表现出饱和动力学，表明它们也是通过受体介导的内吞作用进入巨噬细胞的。正常动物的极低密度脂蛋白（VLDL）以及正常和喂食胆固醇的猴子、大鼠和兔子的低密度脂蛋白（LDL）均未刺激小鼠腹腔巨噬细胞中的胆固醇酯合成。除了对小鼠巨噬细胞的影响外，喂食胆固醇的犬类和兔子的β-VLDL还刺激了培养的人单核细胞中的胆固醇酯合成。目前的研究结果表明，喂食胆固醇的动物的β-VLDL具有刺激巨噬细胞中胆固醇酯合成和积累的一般特性。
