Studies on the initiation of atherosclerosis

我们一直在继续从小鼠腹膜巨噬细胞中分离氧化LDL受体。然而，从小鼠身上获得的材料非常有限。因此，我们将小鼠改为兔，分离腹腔巨噬细胞和Kupffer细胞，并从这些细胞中鉴定氧化LDL受体。乙酰化LDL与氧化LDL的交叉竞争分析表明，兔巨噬细胞具有两种修饰的LDL受体；一种对乙酰低密度脂蛋白有特异性，另一种对氧化低密度脂蛋白和乙酰低密度脂蛋白都有特异性。另一方面，Kupffer细胞具有特异性识别氧化LDL的受体。其分子量约为140KDa。我们现在分离这种蛋白质。然而，在库普弗呼叫中不存在特异性的乙酰- ldl受体。我们发现不仅LDL颗粒，HDL颗粒也被Cu^<++>氧化。由于载脂蛋白的变性，氧化HDL对泡沫细胞中胆固醇酯的降低效果减弱。最近，我们用烟雾提取物培养HDL颗粒，并从巨噬细胞衍生的泡沫细胞中检测其胆固醇-酯外排的特性。当高密度脂蛋白颗粒，特别是载脂蛋白A-1被烟雾提取物修饰时。它们失去了泡沫细胞中胆固醇-酯外排的活性。因此，这些结果表明HDL颗粒中的载脂蛋白A-1对泡沫细胞中胆固醇酯的外排至关重要。最后表明氧化LDL的成分之一溶磷脂酰胆碱可诱导内皮细胞巨噬细胞趋化蛋白-1 (MOP-1) mRNA的表达。此外，据Kume等报道，我们证实了溶磷脂酰胆碱诱导内皮细胞中ICAM-U mRNA的基因表达。但溶磷脂酰胆碱对MCP-1 mRNA和ICAM-1 mRNA表达的时间、过程和剂量依赖性有较大差异。因此，目前正在调查这些事件的详细机制。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