EXPRESSION OF TYPE-I AND TYPE-II BOVINE SCAVENGER RECEPTORS IN CHINESE-HAMSTER OVARY CELLS - LIPID DROPLET ACCUMULATION AND NONRECIPROCAL CROSS COMPETITION BY ACETYLATED AND OXIDIZED LOW-DENSITY-LIPOPROTEIN
EXPRESSION OF TYPE-I AND TYPE-II BOVINE SCAVENGER RECEPTORS IN CHINESE-HAMSTER OVARY CELLS - LIPID DROPLET ACCUMULATION AND NONRECIPROCAL CROSS COMPETITION BY ACETYLATED AND OXIDIZED LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1073/pnas.88.11.4931
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
KRIEGER, M
中科院分区：
文献类型：
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作者：
FREEMAN, M;EKKEL, Y;KRIEGER, M
I型和II型清道夫受体与动脉粥样硬化和其他巨噬细胞相关功能的发展有关，其区别仅在于I型受体中存在富含胞外半胱氨酸的C-末端结构域。 已经产生了表达高水平的I型或II型牛清道夫受体的稳定的中国仓鼠卵巢（CHO）细胞转染子。 I型和II型受体在这些细胞介导的高亲和力饱和的内吞作用的I-125标记的乙酰化低密度脂蛋白（LDL）和I-125标记的氧化LDL与清道夫受体的独特的广泛的配体特异性特征。 与乙酰化LDL孵育2天后，转染细胞积累油红O染色脂滴，使人联想到巨噬细胞泡沫细胞中的脂滴，而未转染的CHO细胞没有。 因此，修饰LDL诱导的细胞内脂质蓄积不需要巨噬细胞特异性基因产物而不是清道夫受体。 在转染细胞中，乙酰化LDL有效地竞争其自身的内吞作用和氧化LDL的内吞作用。 与此相反，氧化LDL有效地竞争自己的内吞作用，但只有差的乙酰化LDL。 这种非互惠的交叉竞争表明，这些配体可以结合到一个单一的受体上的不相同，但相互作用的网站。 表达I型或II型清道夫受体的转染子的结果相似。 因此，以前报道的非互惠交叉竞争培养的腹腔巨噬细胞可能不是I型和II型受体之间的差异的结果。 在转染的CHO细胞中观察到的非互惠交叉竞争不同于先前在培养的巨噬细胞中观察到的。
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 I-125-labeled acetylated low density lipoprotein (LDL) and I-125-labeled oxidized LDL with the distinctive broad ligand specificity characteristic of scavenger receptors. After incubation for 2 days with acetylated LDL, the transfected cell 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.