Freeman M, Ekkel Y, Rohrer L, Penman M, Freedman N J, Chisolm G M, Krieger M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4931-5. doi: 10.1073/pnas.88.11.4931.
Type I and type II scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-associated functions, differ only by the presence in the type I receptor of an extracellular cysteine-rich C-terminal domain. Stable Chinese hamster ovary (CHO) cell transfectants expressing high levels of either the type I or type II bovine scavenger receptors have been generated. Type I and type II receptors in these cells mediated high-affinity saturable endocytosis of both 125I-labeled acetylated low density lipoprotein (LDL) and 125I-labeled oxidized LDL with the distinctive broad ligand specificity characteristic of scavenger receptors. After incubation for 2 days with acetylated LDL, the transfected cells accumulated oil red O-staining lipid droplets reminiscent of those in macrophage foam cells, whereas untransfected CHO cells did not. Thus, macrophage-specific gene products other than the scavenger receptor are not required for modified-LDL-induced intracellular lipid accumulation. In transfected cells, acetylated LDL efficiently competed for both its own endocytosis and that of oxidized LDL. In contrast, oxidized LDL competed effectively for its own endocytosis but only poorly for that of acetylated LDL. This nonreciprocal cross competition suggests that these ligands may bind to nonidentical but interacting sites on a single receptor. Results were similar for transfectants expressing either type I or type II scavenger receptors. Therefore, the nonreciprocal cross competition previously reported for cultured peritoneal macrophages may not be the result of differences between the type I and type II receptors. The nonreciprocal cross competition seen in the transfected CHO cells differs from that previously observed with cultured macrophages.
I 型和 II 型清道夫受体与动脉粥样硬化的发展及其他巨噬细胞相关功能有关,它们的区别仅在于 I 型受体存在一个富含半胱氨酸的细胞外 C 末端结构域。已经构建了稳定表达高水平 I 型或 II 型牛清道夫受体的中国仓鼠卵巢(CHO)细胞转染子。这些细胞中的 I 型和 II 型受体介导了 125I 标记的乙酰化低密度脂蛋白(LDL)和 125I 标记的氧化 LDL 的高亲和力饱和内吞作用,具有清道夫受体独特的广泛配体特异性特征。用乙酰化 LDL 孵育 2 天后,转染细胞积累了油红 O 染色的脂滴,类似于巨噬细胞泡沫细胞中的脂滴,而未转染的 CHO 细胞则没有。因此,修饰 LDL 诱导的细胞内脂质积累不需要清道夫受体以外的巨噬细胞特异性基因产物。在转染细胞中,乙酰化 LDL 有效地竞争其自身的内吞作用以及氧化 LDL 的内吞作用。相反,氧化 LDL 有效地竞争其自身的内吞作用,但对乙酰化 LDL 的内吞作用竞争较弱。这种非相互交叉竞争表明这些配体可能结合在单个受体上不同但相互作用的位点。表达 I 型或 II 型清道夫受体的转染子得到了相似的结果。因此,先前报道的培养腹膜巨噬细胞的非相互交叉竞争可能不是 I 型和 II 型受体之间差异的结果。转染的 CHO 细胞中观察到的非相互交叉竞争与先前在培养巨噬细胞中观察到的不同。