MONONUCLEAR LEUKOCYTES EXPOSED TO OXIDIZED LOW-DENSITY-LIPOPROTEIN SECRETE A FACTOR THAT STIMULATES ENDOTHELIAL-CELLS TO EXPRESS ADHESION MOLECULES
MONONUCLEAR LEUKOCYTES EXPOSED TO OXIDIZED LOW-DENSITY-LIPOPROTEIN SECRETE A FACTOR THAT STIMULATES ENDOTHELIAL-CELLS TO EXPRESS ADHESION MOLECULES
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DOI：
10.1016/0021-9150(93)90264-u
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发表时间：
1993-11-01
期刊：
影响因子：
5.3
通讯作者：
NILSSON, J
中科院分区：
文献类型：
--
作者：
FROSTEGARD, J;WU, RH;NILSSON, J
在喂食高胆固醇饮食的动物中，单核白细胞附着在动脉内皮细胞上，先于动脉粥样硬化的发展。早期病变开始发展为单核细胞迁移到内膜和摄取脂质。这些脂质的主要部分被认为是来自氧化修饰的低密度脂蛋白（LDL）。在本研究中，我们证明，暴露于低浓度的铜氧化低密度脂蛋白的人单核白细胞分泌一个或几个因素，刺激细胞间粘附分子-1（ICAM-1，CD 54），血管细胞粘附分子（VCAM-1）和内皮细胞选择素（E-选择素-1，ELAM-1）的表达，而天然低密度脂蛋白被发现是没有影响。内皮细胞暴露于含有氧化LDL的非条件培养基中不影响粘附分子的表达。培养内皮细胞与条件培养基从单核细胞生长在氧化LDL的存在下，也导致在3倍的单核细胞样U937细胞的结合增加。目前的研究结果表明，单核白细胞暴露于氧化修饰的低密度脂蛋白在早期动脉粥样硬化病变可能会刺激其他白细胞的招聘分泌细胞因子诱导内皮细胞上的粘附分子的表达。
In animals fed a hypercholesterolemic diet, development of artherosclerosis is preceded by attachment of mononuclear leukocytes to the arterial endothelium. Early lesions begin to develop as monocytes migrate into the intima and ingest lipids. A major part of these lipids is believed to be derived from oxidatively modified low density lipoprotein (LDL). In the present study we demonstrate that human mononuclear leukocytes exposed to low concentrations of copper-oxidized LDL secrete one or several factors that stimulate the expression of intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule (VCAM-1) and endothelial selectin (E-selectin-1, ELAM-1), whereas native LDL was found to be without effect. Exposure of endothelial cells to non-conditioned medium containing oxidized LDL did not influence the expression of adhesion molecules. Incubation of endothelial cells with conditioned medium from mononuclear cells grown in the presence of oxidized LDL also resulted in a three-fold increase in the binding of monocytoid U937 cells. The present findings suggest that mononuclear leukocytes exposed to oxidatively modified LDL in early atherosclerotic lesions may stimulate the recruitment of other leukocytes by secreting cytokines which induce the expression of adhesion molecules on the endothelium.