de Beer Maria C, Zhao Zhenze, Webb Nancy R, van der Westhuyzen Deneys R, de Villiers Willem J S
Department of Internal Medicine, University of Kentucky Medical Center, Lexington 40536, USA.
J Lipid Res. 2003 Apr;44(4):674-85. doi: 10.1194/jlr.M200444-JLR200. Epub 2003 Jan 16.
Murine macrosialin (MS), a scavenger receptor family member, is a heavily glycosylated transmembrane protein expressed predominantly in macrophage late endosomes. MS is also found on the cell surface where it is suggested, on the basis of ligand blotting, to bind oxidized LDL (oxLDL). Here we report on the regulation of MS by an atherogenic high-fat diet and oxLDL, and on the inability of MS in transfected cells to bind oxLDL. MS expression was markedly increased in the livers of atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant C3H/HeJ mice fed an atherogenic high-fat diet. In resident-mouse peritoneal macrophages, treatment with oxLDL upregulated MS mRNA and protein expression 1.5- to 3-fold. MS, overexpressed in COS-7 cells through adenovirus mediated gene transfer, bound oxLDL by ligand blotting. However, no binding of oxLDL to MS was observed in intact transfected COS-7 and Chinese hamster ovary cells, despite significant cell surface expression of MS. Furthermore, inhibition of MS through gene silencing did not affect the binding of oxLDL to macrophages. We conclude that although MS expression in macrophages and Kupffer cells is responsive to a proatherogenic inflammatory diet and to oxLDL, MS does not function as an oxLDL receptor on the cell surface.
小鼠巨噬细胞清道夫受体（MS）是清道夫受体家族成员，是一种高度糖基化的跨膜蛋白，主要在巨噬细胞晚期内体中表达。在细胞表面也发现有MS，基于配体印迹分析表明它能结合氧化型低密度脂蛋白（oxLDL）。在此我们报告了致动脉粥样硬化的高脂饮食和oxLDL对MS的调节作用，以及转染细胞中的MS无法结合oxLDL。在喂食致动脉粥样硬化高脂饮食的动脉粥样硬化易感C57BL/6小鼠和动脉粥样硬化抗性C3H/HeJ小鼠的肝脏中，MS表达显著增加。在小鼠腹腔巨噬细胞中，用oxLDL处理可使MS mRNA和蛋白表达上调1.5至3倍。通过腺病毒介导的基因转移在COS-7细胞中过表达的MS，经配体印迹分析可结合oxLDL。然而，在完整的转染COS-7细胞和中国仓鼠卵巢细胞中，尽管MS在细胞表面有大量表达，但未观察到oxLDL与MS的结合。此外，通过基因沉默抑制MS并不影响oxLDL与巨噬细胞的结合。我们得出结论，尽管巨噬细胞和库普弗细胞中的MS表达对促动脉粥样硬化的炎性饮食和oxLDL有反应，但MS在细胞表面并不作为oxLDL受体发挥作用。
