Frostegård J, Nilsson J, Haegerstrand A, Hamsten A, Wigzell H, Gidlund M
Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1990 Feb;87(3):904-8. doi: 10.1073/pnas.87.3.904.
Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipoprotein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LeuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more-differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.
高胆固醇血症是动脉粥样硬化发生的主要危险因素。在喂食高胆固醇饮食的实验动物中，单核细胞黏附于动脉内皮并渗入内膜，在那里它们分化为巨噬细胞并摄取脂质，从而形成脂肪条纹，这是最早类型的动脉粥样硬化斑块。巨噬细胞对正常低密度脂蛋白（LDL）的受体表达很少，但可通过清道夫受体摄取氧化型LDL。本研究旨在探讨氧化型LDL在募集内膜常驻巨噬细胞中的可能作用。我们发现，氧化型LDL可诱导人单核细胞和U937细胞（一个成熟的单核细胞分化研究系统）上主要组织相容性复合体II类分子的表达增强。氧化型LDL还可诱导表面抗原LeuM3的表达增强，但导致CD4抗原的表达降低，这种模式与更分化的巨噬细胞样表型的表达相符。氧化型LDL还可引发单核细胞和U937细胞的聚集，并刺激U937细胞与培养的内皮细胞黏附。结果表明，氧化型LDL可能通过诱导单核细胞黏附于动脉内膜以及刺激内膜单核细胞分化为常驻巨噬细胞，从而促进动脉粥样硬化的发展。
