Minami M, Kume N, Shimaoka T, Kataoka H, Hayashida K, Akiyama Y, Nagata I, Ando K, Nobuyoshi M, Hanyuu M, Komeda M, Yonehara S, Kita T
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, and Institute for Virus Research, Kyoto University, Kyoto, Japan.
Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1796-800. doi: 10.1161/hq1001.096652.
Receptor-mediated endocytosis of oxidized low density lipoprotein (Ox-LDL) by macrophages and the subsequent foam cell transformation in the arterial intima are key events in early atherogenesis. Recently, we have identified a novel macrophage cell-surface receptor for Ox-LDL by expression cloning from a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, designated as the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). Here, we examined SR-PSOX expression in human atherosclerotic lesions. Total cellular RNA and fresh frozen sections were prepared from human carotid endarterectomy specimens (from 21 patients) and directional coronary atherectomy specimens (from 11 patients). Fragments of human aortas of 2 patients without visible atherosclerotic lesions served as negative controls. Quantitative reverse transcription-polymerase chain reaction demonstrated that SR-PSOX mRNA expression was prominent in atherosclerotic lesions but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was predominantly expressed by lipid-laden macrophages in the intima of atherosclerotic plaques in carotid endarterectomy and directional coronary atherectomy specimens, although its expression was not detectable in normal arterial wall. Double-labeled immunohistochemistry confirmed that SR-PSOX is expressed by intimal macrophages. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and thus may play important roles in human atherosclerotic lesion formation.
巨噬细胞对氧化型低密度脂蛋白（Ox-LDL）的受体介导内吞作用以及随后动脉内膜中泡沫细胞的转变是早期动脉粥样硬化形成的关键事件。最近，我们通过从佛波酯12-肉豆蔻酸酯13-乙酸酯刺激的THP-1细胞的cDNA文库中进行表达克隆，鉴定出一种新的Ox-LDL巨噬细胞表面受体，命名为磷脂酰丝氨酸和氧化脂蛋白清除受体（SR-PSOX）。在此，我们检测了SR-PSOX在人类动脉粥样硬化病变中的表达。从人类颈动脉内膜切除术标本（21例患者）和定向冠状动脉粥样斑块切除术标本（11例患者）中制备总细胞RNA和新鲜冰冻切片。选取2例无明显动脉粥样硬化病变的人类主动脉片段作为阴性对照。定量逆转录-聚合酶链反应表明，SR-PSOX mRNA表达在动脉粥样硬化病变中显著，但在正常主动脉中未检测到。免疫组织化学显示，在颈动脉内膜切除术和定向冠状动脉粥样斑块切除术标本的动脉粥样硬化斑块内膜中，SR-PSOX主要由富含脂质的巨噬细胞表达，尽管在正常动脉壁中未检测到其表达。双重标记免疫组织化学证实内膜巨噬细胞表达SR-PSOX。综上所述，SR-PSOX可能参与体内巨噬细胞对Ox-LDL的摄取以及随后的泡沫细胞转变，因此可能在人类动脉粥样硬化病变形成中起重要作用。
