PMID- 9353321 OWN - NLM STAT- MEDLINE DCOM- 19971212 LR - 20220408 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 272 IP - 45 DP - 1997 Nov 7 TI - Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. PG - 28568-73 AB - 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 Gi-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 Kd 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-1 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. FAU - Schecter, A D AU - Schecter AD AD - Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York 10029, USA. FAU - Rollins, B J AU - Rollins BJ FAU - Zhang, Y J AU - Zhang YJ FAU - Charo, I F AU - Charo IF FAU - Fallon, J T AU - Fallon JT FAU - Rossikhina, M AU - Rossikhina M FAU - Giesen, P L AU - Giesen PL FAU - Nemerson, Y AU - Nemerson Y FAU - Taubman, M B AU - Taubman MB LA - eng GR - HL 54469/HL/NHLBI NIH HHS/United States GR - HL09402/HL/NHLBI NIH HHS/United States GR - HL29019/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 9035-58-9 (Thromboplastin) RN - EC 2.7.11.13 (Protein Kinase C) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Arteriosclerosis/metabolism MH - Calcium/metabolism MH - Cell Line MH - Chemokine CCL2/*pharmacology MH - Enzyme Activation MH - Humans MH - Monocytes/*drug effects/metabolism MH - Muscle, Smooth, Vascular/*drug effects/metabolism MH - Protein Kinase C/metabolism MH - RNA, Messenger/metabolism MH - Rabbits MH - Signal Transduction MH - Thromboplastin/genetics/*metabolism MH - Thrombosis/metabolism EDAT- 1997/11/14 00:00 MHDA- 1997/11/14 00:01 CRDT- 1997/11/14 00:00 PHST- 1997/11/14 00:00 [pubmed] PHST- 1997/11/14 00:01 [medline] PHST- 1997/11/14 00:00 [entrez] AID - S0021-9258(18)38693-9 [pii] AID - 10.1074/jbc.272.45.28568 [doi] PST - ppublish SO - J Biol Chem. 1997 Nov 7;272(45):28568-73. doi: 10.1074/jbc.272.45.28568.