OXIDIZED LDL BINDS TO CD36 ON HUMAN MONOCYTE-DERIVED MACROPHAGES AND TRANSFECTED CELL-LINES - EVIDENCE IMPLICATING THE LIPID MOIETY OF THE LIPOPROTEIN AS THE BINDING-SITE
OXIDIZED LDL BINDS TO CD36 ON HUMAN MONOCYTE-DERIVED MACROPHAGES AND TRANSFECTED CELL-LINES - EVIDENCE IMPLICATING THE LIPID MOIETY OF THE LIPOPROTEIN AS THE BINDING-SITE
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DOI：
10.1161/01.atv.15.2.269
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发表时间：
1995-02-01
影响因子：
8.7
通讯作者：
SILVERSTEIN, RL
中科院分区：
文献类型：
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作者：
NICHOLSON, AC;FRIEDA, S;SILVERSTEIN, RL
越来越多的证据表明氧化型低密度脂蛋白（Ox-LDL）参与了动脉粥样硬化的发病机制。已经鉴定了几种结合和内化Ox-LDL的受体，但它们在体内的相对重要性尚不清楚。CD 36是一种88-kD的跨膜糖蛋白，在单核细胞/巨噬细胞、血小板和微血管内皮上表达，被认为是Ox-LDL的假定受体。我们证明，抗CD 36单克隆抗体抑制50%的特异性结合和26%的特异性降解Ox-LDL的人单核细胞衍生的巨噬细胞。为了更全面地描述这种结合，我们在稳定转染人CD 36 cDNA的小鼠NIH-3 T3细胞中评价了CD 36和Ox-LDL之间的相互作用。Ox-LDL以可饱和的方式与CD 36转染的3 T3细胞结合。特异性结合，内化，氧化低密度脂蛋白的降解增加四倍，在CD 36转染的细胞系相比，3 T3细胞转染载体单独。Ox-LDL与CD 36转染的3 T3细胞的结合被一组抗CD 36抗体和可溶性CD 36抑制，但不被血小板反应蛋白抑制。通过LDL和乙酰化LDL与对照和CD 36转染的3 T3细胞的等效结合证明了结合的特异性。由CD 36识别的Ox-LDL上的一个或多个表位是不确定的。两个观察结果表明，CD 36识别脂质部分或脂蛋白的脂质部分是必不可少的载脂蛋白识别。第一种是Ox-LDL与CD 36转染的3 T3细胞的结合增加被脂蛋白的脱脂所消除，第二种是油酸竞争Ox-LDL与CD 36转染的3 T3细胞的结合。这些数据表明，CD 36的功能作为一种Ox-LDL受体，并表明，CD 36可能发挥功能的作用，在脂质积累的人巨噬细胞和随后的泡沫细胞发展动脉粥样硬化。
Accumulating evidence strongly implicates oxidized LDL (Ox-LDL) in the pathogenesis of atherosclerosis. Several receptors have been identified that bind and internalize Ox-LDL, but their relative importance in vivo is unclear. CD36 is an 88-kD transmembrane glycoprotein expressed on monocytes/macrophages, platelets, and microvascular endothelium that has been implicated as a putative receptor for Ox-LDL. We demonstrate that an anti-CD36 monoclonal antibody inhibited 50% of the specific binding and 26% of the specific degradation of Ox-LDL by human monocyte-derived macrophages. To characterize more completely this binding we evaluated interactions between CD36 and Ox-LDL in murine NIH-3T3 cells stably transfected with human CD36 cDNA. Ox-LDL bound to CD36-transfected 3T3 cells in a saturable manner. Specific binding, internalization, and degradation of Ox-LDL were increased fourfold in CD36-transfected cell lines compared with 3T3 cells transfected with vector alone. Binding of Ox-LDL to CD36-transfected 3T3 cells was inhibited by a panel of anti-CD36 antibodies and by soluble CD36 but not by thrombospondin. Specificity of binding was demonstrated by the equivalent binding of LDL and acetylated LDL to control and CD36-transfected 3T3 cells. The epitope or epitopes on Ox-LDL recognized by CD36 are undefined. Two observations suggest that CD36 recognizes a lipid moiety or that the lipid portion of the lipoprotein is essential for apoprotein recognition. The first is that the increased binding of Ox-LDL to CD36-transfected 3T3 cells is abrogated by delipidation of the lipoprotein, and the second is that oleic acid competes for the binding of Ox-LDL to CD36-transfected 3T3 cells. These data demonstrate that CD36 functions as an Ox-LDL receptor and suggest that CD36 may play a functional role in lipid accumulation by human macrophages and subsequent foam cell development during atherosclerosis.