Mori N, Yamada N, Ishibashi S, Kawakami M, Takahashi K, Shimano H, Fujisawa M, Takaku F, Murase T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Biochim Biophys Acta. 1987 Nov 21;922(2):103-10. doi: 10.1016/0005-2760(87)90143-3.
We have previously shown that cultured rat alveolar macrophages synthesize and secrete lipoprotein lipase into the medium. The purpose of the present experiments is to examine whether cholesterol-enriched lipoproteins from cholesterol-fed animals have any effects on the lipoprotein lipase secretion and the lipid accumulation in macrophages. Macrophages incubated with the VLDL obtained from rats fed a normal diet secreted 2-fold higher amounts of lipoprotein lipase than those without lipoproteins. Intermediate-, low- and very-low-density lipoproteins from rats fed a high-cholesterol diet also enhanced the lipoprotein lipase secretion. Normal high- and low-density lipoproteins, and high-density lipoproteins from hypercholesterolemic animals did not cause any increase in the lipoprotein lipase secretion. The lipoproteins which stimulated the lipoprotein lipase secretion caused intracellular accumulation of both triacylglycerol and cholesterol. It is speculated that macrophages residing in the environment rich in lipoproteins, especially hypercholesterolemic lipoproteins, take them up and accumulate lipids intracellularly, and that this process links with the lipoprotein lipase secretion. The secreted lipoprotein lipase could facilitate, by degrading lipoproteins, the uptake of lipoprotein lipase-modified lipoproteins. Probably such a series of events is of importance in the foam cell formation of macrophages.
我们之前已经表明,培养的大鼠肺泡巨噬细胞可合成脂蛋白脂肪酶并将其分泌到培养基中。本实验的目的是研究来自高胆固醇喂养动物的富含胆固醇的脂蛋白是否对巨噬细胞中脂蛋白脂肪酶的分泌和脂质积累有任何影响。与从正常饮食喂养的大鼠获得的极低密度脂蛋白(VLDL)一起孵育的巨噬细胞分泌的脂蛋白脂肪酶量比未添加脂蛋白的巨噬细胞高出2倍。高胆固醇饮食喂养的大鼠的中密度、低密度和极低密度脂蛋白也增强了脂蛋白脂肪酶的分泌。正常的高密度和低密度脂蛋白以及高胆固醇血症动物的高密度脂蛋白并未导致脂蛋白脂肪酶分泌增加。刺激脂蛋白脂肪酶分泌的脂蛋白会导致细胞内甘油三酯和胆固醇的积累。据推测,存在于富含脂蛋白尤其是高胆固醇血症脂蛋白环境中的巨噬细胞会摄取它们并在细胞内积累脂质,并且这个过程与脂蛋白脂肪酶的分泌相关。分泌的脂蛋白脂肪酶可通过降解脂蛋白促进脂蛋白脂肪酶修饰的脂蛋白的摄取。可能这样一系列事件在巨噬细胞泡沫细胞形成中具有重要意义。