Phillips D R, Arnold K, Innerarity T L
Nature. 1985;316(6030):746-8. doi: 10.1038/316746a0.
Macrophages possess a receptor that binds low-density lipoproteins (LDL) containing lysine residues modified by acetylation (Ac LDL), acetoacetylation (AcAc LDL) or malondialdehyde treatment. This receptor (referred to as the Ac LDL receptor or scavenger receptor) internalizes the bound lipoprotein. As a consequence, massive amounts of cholesteryl esters accumulate so that macrophages in culture resemble foam cells found in atherosclerotic lesions. In an effort to identify an unmodified mammalian macromolecule that binds to the Ac LDL receptor, we investigated whether platelet secretory products affect the receptor-mediated endocytosis of chemically modified lipoproteins. Platelets are a potential source of such activity because they exist in close association with foam cells in developing atherosclerotic lesions. Our study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophages and the subsequent accumulation of cholesteryl esters. This is the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages.
巨噬细胞拥有一种受体，该受体可结合含有经乙酰化（乙酰化低密度脂蛋白，Ac LDL）、β-羟基-β-甲基戊二酸单酰辅酶A （HMG-CoA）还原酶抑制剂、丙二酰辅酶A （MMA-CoA）还原酶抑制剂处理而修饰的赖氨酸残基的低密度脂蛋白（LDL）。这种受体（称为Ac LDL受体或清道夫受体）会将结合的脂蛋白内化。结果，大量胆固醇酯积聚，使得培养中的巨噬细胞类似于动脉粥样硬化病变中发现的泡沫细胞。为了鉴定一种与Ac LDL受体结合的未修饰的哺乳动物大分子，我们研究了血小板分泌产物是否会影响化学修饰脂蛋白的受体介导的内吞作用。血小板是这种活性的潜在来源，因为它们与正在形成的动脉粥样硬化病变中的泡沫细胞紧密相关。我们的研究表明，人血小板分泌一种产物，该产物可抑制小鼠腹腔巨噬细胞对β-羟基-β-甲基戊二酸单酰辅酶A （HMG-CoA）还原酶抑制剂、丙二酰辅酶A （MMA-CoA）还原酶抑制剂的结合和摄取以及随后胆固醇酯的积累。这是内源性大分子与巨噬细胞上的Ac LDL受体相互作用的首个迹象。
