Release of active tissue factor by human arterial smooth muscle cells.
Release of active tissue factor by human arterial smooth muscle cells.
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DOI：
10.1161/01.res.87.2.126
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发表时间：
2000-07
影响因子：
20.1
通讯作者：
A. Schecter;Benjamin Spirn;M. Rossikhina;P. Giesen;V. Bogdanov;J. Fallon;E. A. Fisher;L. Schnapp;Y. Nemerson;M. Taubman
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文献类型：
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作者：
A. Schecter;Benjamin Spirn;M. Rossikhina;P. Giesen;V. Bogdanov;J. Fallon;E. A. Fisher;L. Schnapp;Y. Nemerson;M. Taubman
组织因子（TF），凝血的引发剂，被认为主要在细胞表面起作用。最近的数据表明，活性TF存在于动脉粥样硬化斑块、动脉壁和血液的细胞外。本研究旨在确定平滑肌细胞（SMCs）是否能产生细胞外TF，平滑肌细胞是动脉TF的主要来源。活性TF在培养的人SMCs培养基中积累，约占24小时内底层细胞中测量到的活性TF的10%。血小板衍生生长因子、佛波酯和肿瘤坏死因子- α导致培养基中TF活性增加约3倍。TF在培养基中的释放依赖于TF跨膜结构域的存在，而不是细胞质结构域的存在。针对TF的抗体沉淀了培养基中的大部分活性，而针对β(1)-整合素亚基的抗体沉淀了大约33%的活性。用洗涤剂或磷脂酰丝氨酸处理：磷脂酰胆碱未增加活性，提示SMCs释放的TF均处于适当的脂质环境中，未被加密。Western blotting显示培养基中含有全长TF蛋白。荧光细胞检测显示细胞外TF主要存在于<或=200 nm的颗粒中，其密度为1.10 g/mL。我们假设在受损动脉壁和动脉粥样硬化斑块中发现的活性细胞外TF部分来源于SMC微粒。
Tissue factor (TF), the initiator of coagulation, is thought to function predominantly at the cell surface. Recent data have suggested that active TF is present extracellularly in atherosclerotic plaques, the arterial wall, and the blood. This study was conducted to determine whether smooth muscle cells (SMCs), a major source of arterial TF, could generate extracellular TF. Active TF accumulated in the medium of cultured human SMCs, representing approximately 10% of that measured in the underlying cells at 24 hours. Platelet-derived growth factor, phorbol ester, and tumor necrosis factor-alpha caused approximately 3-fold increases in TF activity in the medium. Release of TF into the medium was dependent on the presence of the TF transmembrane domain but not the cytoplasmic domain. Antibodies to TF precipitated most of the activity from the culture medium, whereas antibodies to the beta(1)-integrin subunit precipitated approximately 33% of the activity. Treatment with detergent or phosphatidylserine:phosphatidylcholine did not increase activity, suggesting that all TF released by SMCs was in the appropriate lipid milieu and not encrypted. Western blotting showed that the medium contained full-length TF protein. Fluorescent cytometry showed that extracellular TF was present largely in particles < or =200 nm, which had a density of 1.10 g/mL. We hypothesize that active extracellular TF found in the injured arterial wall and atherosclerotic plaques derives, in part, from SMC microparticles.