Studies on the initiation of atherosclerosis

我们一直在继续从小鼠腹腔巨噬细胞中分离氧化LDL受体。然而，从小鼠获得的材料相当有限。因此，我们将来源从小鼠改为家兔，分离了腹腔巨噬细胞和枯否细胞，并从这些细胞中鉴定了氧化LDL的受体。乙酰和氧化LDL之间的交叉竞争分析表明，兔巨噬细胞有两种修饰的LDL受体，一种是特异性的乙酰-LDL和其他识别氧化和乙酰-LDL。另一方面，枯否细胞具有特异性识别氧化LDL的受体。其分子量约为140 KDa。我们正在分离这种蛋白质。但Kupffer细胞中不存在乙酰化LDL的特异性受体，我们发现Cu^++不仅能氧化LDL颗粒，而且能氧化HDL颗粒。氧化型HDL由于使载脂蛋白变性，对泡沫细胞胆固醇酯的降低作用减弱， ...更多信息 HDL颗粒中的A-1（PNAS 1991 88 p.6457）。最近，我们孵育HDL颗粒与烟雾提取物，并检查其性质的胆固醇酯流出巨噬细胞源性泡沫细胞。每当HDL颗粒，特别是载脂蛋白A-1，被烟雾提取物修饰时。它们丧失了胆固醇酯从泡沫细胞流出的活性。这些结果表明HDL颗粒中的apoA-1是泡沫细胞胆固醇酯流出所必需的。最后表明氧化LDL的成分之一溶血磷脂酰胆碱诱导内皮细胞巨噬细胞趋化蛋白-1（MOP-1）mRNA的表达。此外，如Kume等所报道的，我们证实溶血磷脂酰胆碱诱导内皮细胞ICAM-1 mRNA的基因表达。但是，溶血磷脂酰胆碱对MCP-1 mRNA和ICAM-1 mRNA表达的时间过程和剂量依赖性是完全不同的。因此，这些事件的详细机制目前正在调查中。少

We have been continuing to isolate receptor for oxidized LDL from mouse peritoneal macrophages. However materials obtained from mouse were quite limited. Therefore we changed the souse from mouse to rabbit and isolated peritoneal macrophages and Kupffer cell and characterized receptors for oxidized LDL from there cells. Cross competition analysis between acetyl and oxidized LDL indicated that rabbit macrophages have two kinds of modified LDL receptors ; one is specific for acetyl-LDL and the other recognizes both oxidized and acetyl-LDL. On the other hand, Kupffer cells have receptor which recognizes oxidized LDL specifically. Its molecular weight is approximately 140KDa. We are now isolating this protein. However, specific receptor for acetyl-LDL does not exist in Kupffer calls.We found that not only LDL particles but also HDL particles were oxidized by Cu^<++>. Oxidized HDL showed a lessened effect on the decrease of cholesteryl ester in foam cells because of the denaturation of apo … More A-1 in HDL particles (PNAS 1991 88 p.6457). Recently we incubated HDL particles with smoke-extracts and checked their property of cholesteryl-ester efflux from macrophages-derived foam cells. Whenever HDL particles, especially apo A-1, are modified by smoke extracts. they loss the activity of cholesteryl-ester efflux from foam cells. Therefore these results indicated that apo A-1 in HDL particles is essential for efflux of cholesteryl ester in foam cells.Finally it is showed that one of the componints of oxidized LDL, lyso-phosphatidyl-choline, induced the expression of macrophage-chemotaxitic protein-1 (MOP-1) mRNA in endothelial cells. In addition as reported by Kume et al,we conformed that lyso-phosphatidyl-choline induced the gene expression of ICAM-U mRNA in endothelial cells. However time course and dose dependency of lyso-phosphatidyl-choline for the expression of both MCP-1 mRNA and ICAM-1 mRNA are quite different. Therefore the detail mechanism of these events are currently under-investigating. Less