MACROPHAGE-DERIVED FOAM CELLS FRESHLY ISOLATED FROM RABBIT ATHEROSCLEROTIC LESIONS DEGRADE MODIFIED LIPOPROTEINS, PROMOTE OXIDATION OF LOW-DENSITY LIPOPROTEINS, AND CONTAIN OXIDATION-SPECIFIC LIPID-PROTEIN ADDUCTS
MACROPHAGE-DERIVED FOAM CELLS FRESHLY ISOLATED FROM RABBIT ATHEROSCLEROTIC LESIONS DEGRADE MODIFIED LIPOPROTEINS, PROMOTE OXIDATION OF LOW-DENSITY LIPOPROTEINS, AND CONTAIN OXIDATION-SPECIFIC LIPID-PROTEIN ADDUCTS
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DOI：
10.1172/jci115006
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发表时间：
1991-01-01
影响因子：
15.9
通讯作者：
WITZTUM, JL
中科院分区：
文献类型：
--
作者：
ROSENFELD, ME;KHOO, JC;WITZTUM, JL
从经球囊去内皮化和饮食诱导的高胆固醇血症造成动脉粥样硬化的家兔动脉中分离出纯的巨噬细胞源性泡沫细胞（MFC）。 在无菌条件下使用酶消化程序和不连续密度梯度离心分离MFC。 MFC制备物的纯度用巨噬细胞特异性单克隆抗体RMA-11进行免疫细胞化学验证。 在含有0.5%FCS的培养基中铺板24小时的MFC含有约600 μ g胆固醇/mg细胞蛋白，其中80%是酯化胆固醇。 MFC特异性降解低密度脂蛋白（LDL），乙酰-LDL，铜氧化的LDL，和β-极低密度脂蛋白（β-VLDL）的速率与小鼠腹腔巨噬细胞（MPM）在5小时测定。 MFC内的部分动脉粥样硬化病变的气球兔以及MFC分离出相同的病变中的抗氧化剂的存在下，表现出阳性免疫反应性与多克隆豚鼠抗血清和小鼠单克隆抗体针对丙二醛-LDL，和4-羟基壬烯醛-LDL。 MFC还表现出诱导LDL氧化的能力，其速率与MPM和兔主动脉内皮细胞所表现出的速率相当。 这些数据提供了直接的证据表明，动脉壁巨噬细胞在体内表达修饰的LDL受体，含有在氧化LDL中发现的表位，并且即使在最大限度地加载胆固醇时也能够氧化LDL。
Pure macrophage-derived foam cells (MFC) were isolated from the aortas of rabbits made atherosclerotic by balloon deendothelialization followed by diet-induced hypercholesterolemia. The MFC were isolated under sterile conditions using an enzymatic digestion procedure and discontinuous density gradient centrifugation. The purity of the MFC preparations was verified immunocytochemically with the macrophage specific monoclonal antibody RMA-11. MFC plated in medium containing 0.5% FCS for 24 h contained approximately 600 mu-g cholesterol per mg cell protein, 80% of which was esterified cholesterol. The MFC specifically degraded low density lipoprotein (LDL), acetyl-LDL, copper oxidized LDL, and beta-very low density lipoprotein (beta-VLDL) at rates comparable to mouse peritoneal macrophages (MPM) in 5-h assays. MFC within sections of the atherosclerotic lesions from the ballooned rabbits as well as the MFC isolated from the same lesions in the presence of antioxidants, exhibited positive immunoreactivity with polyclonal guinea pig antisera and mouse monoclonal antibodies directed against malondialdehyde-LDL, and 4-hydroxynonenal-LDL. The MFC also exhibited the capacity to induce the oxidation of LDL at rates comparable to those exhibited by MPM and rabbit aortic endothelial cells. These data provide direct evidence that arterial wall macrophages express modified LDL receptors in vivo, contain epitopes found in oxidized-LDL and are capable of oxidizing LDL even when maximally loaded with cholesterol.