Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI
Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI
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DOI：
10.1194/jlr.m600136-jlr200
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发表时间：
2006-11-01
影响因子：
6.5
通讯作者：
Rinninger, Franz
中科院分区：
文献类型：
--
作者：
Brundert, May;Heeren, Joerg;Rinninger, Franz
清道夫受体类b型I （SR-BI）介导高密度脂蛋白胆固醇酯（CEs）的选择性摄取并促进未酯化胆固醇的排出。巨噬细胞中SR-BI的表达可能在动脉粥样硬化中起作用。探讨SR-BI在巨噬细胞选择性CE摄取和胆固醇外排中的作用。巨噬细胞和HDL来源于野生型（WT）或SR-BI敲除（KO；纯合子）小鼠。为了摄取，巨噬细胞在含有I-125-/ h -3标记的HDL的培养基中孵育。对于脂质去除，以HDL为受体分析[H-3]胆固醇外排。在WT和SR-BI KO巨噬细胞中，高密度脂蛋白CE （[H-3]胆固醇-油酰醚- i -125-酪胺纤维素糖）的选择性摄取是相似的。放射性标记的SR-BI KO- hdl在WT和SR-BI KO巨噬细胞中的选择性摄取率比WT- hdl低。以HDL为受体的WT和SR-BI KO细胞的胆固醇外排相似。与WT-HDL相比，SR-BI KO-HDL更有效地促进了两种巨噬细胞的胆固醇去除。巨噬细胞选择性地摄取HDL - CE，而不依赖于SR-BI。此外，在巨噬细胞中，存在大量不受SR-BI介导的胆固醇外排。因此，独立于sr - bi的机制介导选择性CE摄取和胆固醇去除。与WT-HDL相比，SR-BI KO-HDL是一种较差的选择性CE摄取供体，而SR-BI KO-HDL更有效地促进胆固醇外排。
Scavenger receptor classBtype I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was explored. Macrophages and HDL originated from wild-type (WT) or SR-BI knockout (KO; homozygous) mice. For uptake, macrophages were incubated in medium containing I-125-/H-3-labeled HDL. For lipid removal, [H-3] cholesterol efflux was analyzed using HDL as acceptor. Selective uptake of HDL CE ([H-3] cholesteryl oleyl ether-I-125-tyramine cellobiose) was similar in WT and SR-BI KO macrophages. Radiolabeled SR-BI KO-HDL yielded a lower rate of selective uptake compared with WT-HDL in WT and SR-BI KO macrophages. Cholesterol efflux was similar in WT and SR-BI KO cells using HDL as acceptor. SR-BI KO-HDL more efficiently promoted cholesterol removal compared with WT-HDL from both types of macrophages. Macrophages selectively take up HDL CE independently of SR-BI. Additionally, in macrophages, there is substantial cholesterol efflux that is not mediated by SR-BI. Therefore, SR-BI-independent mechanisms mediate selective CE uptake and cholesterol removal. SR-BI KO-HDL is an inferior donor for selective CE uptake compared with WT-HDL, whereas SR-BI KO-HDL more efficiently promotes cholesterol efflux.