Mathur S N, Field F J, Megan M B, Armstrong M L
Biochim Biophys Acta. 1985 Mar 27;834(1):48-57. doi: 10.1016/0005-2760(85)90175-4.
Macrophages provide an important way for cholesteryl esters to accumulate in tissues in pathologic amounts. We studied cholesteryl ester metabolism in thioglycollate-induced peritoneal macrophages obtained from normocholesterolemic and hypercholesterolemic rabbits. The macrophage preparations from normocholesterolemic rabbit (MN cells) had 26 nmol esterified cholesterol/mg cellular protein, incorporated 1 nmol of labeled oleate into cholesteryloleate/2 h per mg cellular protein and had an acyl-coenzyme A:cholesterol acyltransferase activity of 22 pmol cholesterylpalmitate formed/min per mg protein in isolated membranes. The macrophage preparations from hypercholesterolemic rabbits (MHC cells) contained a 12-fold greater mass of cholesteryl ester, had an 8-times higher rate of formation of cholesteryloleate, and had 3-times more acyl-coenzyme A:cholesterol acyltransferase activity in the isolated membranes. When a cholesterol acceptor (10% fetal bovine serum or 10 mg of lipid-free fetal bovine serum protein) was added to the culture medium of rabbit MHC cells, the MHC cells retained more than 70% of their cholesteryl esters after 48 h of incubation. In contrast, when a cholesterol acceptor (10% fetal bovine serum) was added to the medium of thioglycollate-induced, cholesterol-enriched macrophages from mice, the mice macrophages retained only 19% of their cholesteryl esters after 48 h of incubation. The limited capacity of rabbit macrophages to release unesterified cholesterol from stored cytoplasmic cholesteryl esters to an exogenous acceptor may be related to the propensity of rabbits to develop atherosclerotic lesions.
巨噬细胞为胆固醇酯在组织中病理性积聚提供了一条重要途径。我们研究了从正常胆固醇血症和高胆固醇血症兔获取的巯基乙酸盐诱导的腹腔巨噬细胞中的胆固醇酯代谢。来自正常胆固醇血症兔的巨噬细胞制剂（MN细胞）含有26 nmol酯化胆固醇/ mg细胞蛋白，每mg细胞蛋白每2小时将1 nmol标记的油酸酯掺入胆固醇油酸酯中，并且在分离的膜中具有22 pmol胆固醇棕榈酸酯形成/分钟每mg蛋白的酰基辅酶A：胆固醇酰基转移酶活性。来自高胆固醇血症兔的巨噬细胞制剂（MHC细胞）含有高12倍的胆固醇酯质量，胆固醇油酸酯形成速率高8倍，并且在分离的膜中具有多3倍的酰基辅酶A：胆固醇酰基转移酶活性。当向兔MHC细胞的培养基中添加胆固醇受体（10％胎牛血清或10 mg无脂胎牛血清蛋白）时，MHC细胞在孵育48小时后保留超过70％的胆固醇酯。相比之下，当向来自小鼠的巯基乙酸盐诱导的、富含胆固醇的巨噬细胞的培养基中添加胆固醇受体（10％胎牛血清）时，小鼠巨噬细胞在孵育48小时后仅保留19％的胆固醇酯。兔巨噬细胞将储存的细胞质胆固醇酯中的未酯化胆固醇释放到外源性受体的能力有限，这可能与兔发生动脉粥样硬化病变的倾向有关。
