Wang G P, Deng Z D, Ni J, Qu Z L
Department of Pathology, Tongji Medical University, Wuhan, People's Republic of China.
Atherosclerosis. 1997 Aug;133(1):31-6. doi: 10.1016/s0021-9150(97)00109-3.
The migration of monocytes into arterial subendothelial space is one of the earliest events in atherogenesis. Monocyte chemoattractant protein 1 (MCP-1) is a potent monocyte chemoattractant. The purpose of this work was to examine whether oxidized low density lipoprotein (OX-LDL) and very low density lipoprotein (OX-VLDL) have any effect on the expression of MCP-1 mRNA and protein in rabbit peritoneal exudate macrophages. The total RNA was extracted from the macrophages after 24 h exposure to LDL, VLDL, OX-LDL, and OX-VLDL, respectively, and the media (LDL-CM, VLDL-CM, OX-LDL-CM and OX-VLDL-CM) conditioned by the macrophages exposed to the above-mentioned lipoproteins were collected. The MCP-1 mRNA expression in macrophages was examined by Northern blot analysis. Meanwhile, MCP-1 protein in the conditioned media was determined by sandwich ELISA. The chemotactic activity of the conditioned media for monocytes was determined by micropore filter assay. The results revealed that the macrophages can express MCP-1, and 24 h exposure to OX-LDL and OX-VLDL induced a 3.2-fold and a 3.4-fold increase in MCP-1 mRNA expression in macrophages and a 2.2-fold and a 2.5-fold increase in the level of MCP-1 protein in the conditioned media, respectively. However, 24 h exposure to LDL and VLDL only induced a slight increase in the expression of MCP-1 mRNA and protein in macrophages. Furthermore, the migration distance of monocyte induced by OX-LDL-CM and OX-VLDL-CM was longer than that induced by LDL-CM and VLDL-CM, as well as by CM. We conclude that the macrophages can express MCP-1, and OX-VLDL and OX-VLDL induce stronger MCP-1 expression. It suggests that macrophages may amplify the recruitment into subendothelial space, and OX-LDL and OX-VLDL may play an important role in the pathogenesis of atherosclerosis through enhancing the MCP-1 expression in macrophages.
单核细胞迁移至动脉内皮下间隙是动脉粥样硬化形成过程中最早出现的事件之一。单核细胞趋化蛋白1(MCP-1)是一种强效的单核细胞趋化因子。本研究旨在探讨氧化型低密度脂蛋白(OX-LDL)和氧化型极低密度脂蛋白(OX-VLDL)对兔腹腔渗出巨噬细胞中MCP-1 mRNA和蛋白表达是否有影响。分别将巨噬细胞暴露于低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、OX-LDL和OX-VLDL 24小时后提取总RNA,并收集经上述脂蛋白处理的巨噬细胞所产生的培养基(LDL-CM、VLDL-CM、OX-LDL-CM和OX-VLDL-CM)。通过Northern印迹分析检测巨噬细胞中MCP-1 mRNA的表达。同时,采用夹心ELISA法测定培养基中MCP-1蛋白的含量。采用微孔滤膜法测定培养基对单核细胞的趋化活性。结果显示,巨噬细胞能够表达MCP-1,暴露于OX-LDL和OX-VLDL 24小时可使巨噬细胞中MCP-1 mRNA表达分别增加3.2倍和3.4倍,培养基中MCP-1蛋白水平分别增加2.2倍和2.5倍。然而,暴露于LDL和VLDL 24小时仅使巨噬细胞中MCP-1 mRNA和蛋白表达略有增加。此外,OX-LDL-CM和OX-VLDL-CM诱导单核细胞的迁移距离长于LDL-CM、VLDL-CM以及空白培养基(CM)诱导的迁移距离。我们得出结论,巨噬细胞能够表达MCP-1,且OX-VLDL和OX-LDL诱导MCP-1表达的能力更强。这表明巨噬细胞可能会扩大向内皮下间隙的募集,而OX-LDL和OX-VLDL可能通过增强巨噬细胞中MCP-1的表达在动脉粥样硬化的发病机制中发挥重要作用。