Podrez Eugene A, Poliakov Eugenia, Shen Zhongzhou, Zhang Renliang, Deng Yijun, Sun Mingjiang, Finton Paula J, Shan Lian, Febbraio Maria, Hajjar David P, Silverstein Roy L, Hoff Henry F, Salomon Robert G, Hazen Stanley L
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Biol Chem. 2002 Oct 11;277(41):38517-23. doi: 10.1074/jbc.M205924200. Epub 2002 Jul 26.
The macrophage scavenger receptor CD36 plays an important role in binding and uptake of oxidized forms of low-density lipoprotein (LDL), foam cell formation, and lesion development during atherosclerosis. The structural basis of CD36-lipoprotein ligand recognition is an area of intense interest. In a companion article we reported the characterization of a structurally conserved family of oxidized choline glycerophospholipids (oxPC(CD36)) that serve as novel high affinity ligands for cells stably transfected with CD36, mediating recognition of multiple oxidized forms of LDL (Podrez, E. A., Poliakov, E., Shen, Z., Zhang, R., Deng, Y., Sun, M., Finton, P., Shan, L., Gugiu, B., Fox, P. L., Hoff, H. F., Salomon, R. G., and Hazen, S. L. (July 8, 2002) J. Biol. Chem. 277, 10.1074/jbc.M203318200). Here we use macrophages from wild-type and CD36 null mice to demonstrate that CD36 is the major receptor on macrophages mediating recognition of oxPC(CD36) species when presented (+/- plasma) in pure form, within PC bilayers in small unilamellar vesicles, and within liposomes generated from lipid extracts of native LDL. We also show that oxPC(CD36) promote CD36-dependent recognition when present at only a few molecules per particle, resulting in macrophage binding, uptake, metabolism, cholesterol accumulation, and foam cell formation. Finally, using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we demonstrate that oxPC(CD36) are generated in vivo and are enriched in atherosclerotic lesions. Collectively, our data suggest that formation of this novel family of oxidized phospholipids participates in CD36-mediated recognition of oxidized lipoproteins and foam cell formation in vivo.
巨噬细胞清道夫受体CD36在动脉粥样硬化过程中对氧化型低密度脂蛋白（LDL）的结合与摄取、泡沫细胞形成以及病变发展起着重要作用。CD36与脂蛋白配体识别的结构基础是一个备受关注的领域。在一篇相关文章中，我们报道了一类结构保守的氧化胆碱甘油磷脂（oxPC(CD36)）家族的特性，它们作为新型高亲和力配体，可与稳定转染CD36的细胞结合，介导对多种氧化形式LDL的识别（波德雷兹，E.A.，波利雅科夫，E.，沈，Z.，张，R.，邓，Y.，孙，M.，芬顿，P.，单，L.，古吉乌，B.，福克斯，P.L.，霍夫，H.F.，所罗门，R.G.，和哈森，S.L.（2002年7月8日）《生物化学杂志》277卷，10.1074/jbc.M203318200）。在此，我们使用野生型和CD36基因敲除小鼠的巨噬细胞来证明，当以纯形式呈现（±血浆）、存在于小单层囊泡的磷脂双层中以及存在于源自天然LDL脂质提取物的脂质体中时，CD36是巨噬细胞上介导对oxPC(CD36)种类识别的主要受体。我们还表明，当每个颗粒仅存在少数几个分子时，oxPC(CD36)可促进CD36依赖性识别，从而导致巨噬细胞结合、摄取、代谢、胆固醇积累以及泡沫细胞形成。最后，使用高效液相色谱与在线电喷雾电离串联质谱（LC/ESI/MS/MS），我们证明oxPC(CD36)在体内生成并在动脉粥样硬化病变中富集。总体而言，我们的数据表明，这个新型氧化磷脂家族的形成参与了CD36介导的体内氧化脂蛋白识别和泡沫细胞形成。
