Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells
Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells
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DOI：
10.1074/jbc.272.45.28568
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发表时间：
1997-11-07
影响因子：
4.8
通讯作者：
Taubman, MB
中科院分区：
文献类型：
--
作者：
Schecter, AD;Rollins, BJ;Taubman, MB
单核细胞趋化蛋白-1(MCP-1)是一种C-C趋化因子，被认为在将单核细胞募集到动脉粥样硬化斑块中发挥重要作用。组织因子(TF)是凝血的起始者，存在于动脉粥样硬化斑块、巨噬细胞和人的主动脉平滑肌细胞(SMC)中。斑块破裂时TF暴露可能导致急性血栓形成，导致心肌梗死和中风。本报告证明MCP-1可诱导SMC和THP-1粒单核细胞中TFmRNA和蛋白的积聚。MCP-1还可诱导人SMC表面的转铁蛋白活性。百日咳毒素可抑制MCP-1对SMC转铁蛋白的诱导作用，提示SMC MCP-1受体与G(I)-蛋白偶联。细胞内钙离子的螯合和蛋白激酶C的抑制阻断了MCP-1对Tf的诱导，提示SMC通过激活磷脂酶C与MCP-1结合K-d，这与先前报道的巨噬细胞类似。然而，编码巨噬细胞MCP-1受体CCR2A和B的mRNA在SMC中不存在，表明它们具有独特的MCP-1受体。这些数据表明，除了作为一种趋化物质，MCP-I可能还具有促凝血功能，并增加了SMC和巨噬细胞分泌的MCP-1在这些细胞中诱导TF活性的自分泌途径的可能性。
Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine thought to play a major role in recruiting monocytes to the atherosclerotic plaque. Tissue factor (TF), the initiator of coagulation, is found in the atherosclerotic plaque, macrophages, and human aortic smooth muscle cells (SMC). The exposure of TF during plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the accumulation of TF mRNA and protein in SMC and in THP-1 myelomonocytic leukemia cells. MCP-1 also induces TF activity on the surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled to a G(i)-protein. Chelation of intracellular calcium and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a K-d similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that they possess a distinct MCP-1 receptor. These data suggest that in addition to being a chemoattractant, MCP-I may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells.