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

被引:206
作者
FREEMAN, M
EKKEL, Y
ROHRER, L
PENMAN, M
FREEDMAN, NJ
CHISOLM, GM
KRIEGER, M
机构
[1] MIT,DEPT BIOL,E25-236,CAMBRIDGE,MA 02139
[2] CLEVELAND CLIN FDN,RES INST,DEPT VASC CELL BIOL & ATHEROSCLEROSIS,CLEVELAND,OH 44195
[3] MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114
关键词
ATHEROSCLEROSIS; FOAM CELLS; LIGAND BINDING;
D O I
10.1073/pnas.88.11.4931
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4931 / 4935
页数:5
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