Scavenger receptor SR-BI in macrophage lipid metabolism.
Scavenger receptor SR-BI in macrophage lipid metabolism.
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巨噬细胞脂质代谢中的清除剂受体SR-BI。
DOI：
10.1016/j.atherosclerosis.2011.03.017
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发表时间：
2011-07
期刊：
影响因子：
5.3
通讯作者：
van der Westhuyzen, Deneys R.
中科院分区：
文献类型：
--
作者：
Ji, Ailing;Meyer, Jason M.;Cai, Lei;Akinmusire, Akinwunmi;de Beer, Maria C.;Webb, Nancy R.;van der Westhuyzen, Deneys R.
探讨巨噬细胞清道夫受体BI（SR-BI）调节巨噬细胞胆固醇稳态和抗动脉粥样硬化的机制。本实验研究了SR-BI在体外培养的小鼠骨髓源性巨噬细胞（BMM）中的表达和功能。SR-BI，其他清道夫受体SRA和CD 36和ATP结合盒转运蛋白ABCA 1和ABCG 1在BMM分化过程中分别受到明显调控。SR-BI水平在培养过程中短暂增加至显著水平。SR-BI在BMM中的表达通过用修饰的LDL进行脂质负载而可逆地下调; SR-BI被证明存在于细胞表面以及细胞内。BMM表现出选择性HDL CE摄取，然而，这不依赖于SR-BI或另一种潜在的候选糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1（GPIHBP 1）。SR-BI在促进非脂质负载细胞中胆固醇的双向流动中起重要作用。SR-BI表达增强细胞胆固醇流出和HDL胆固醇流入，但不导致改变细胞胆固醇质量。SR-BI依赖性外排发生在较大的HDL颗粒，但不发生在较小的HDL 3。胆固醇负荷后，ABCA 1和ABCG 1上调，并作为胆固醇流出的主要贡献者，而SR-BI表达下调。我们的研究结果表明，SR-BI在巨噬细胞胆固醇通量中起着重要作用，这可能部分解释了其对动脉粥样硬化形成的影响。
To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. The expression and function of SR-BI, was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL3. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.
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