期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 30, 期 9, 页码 1818-U313出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.110.209577
关键词
apoptosis; coagulation; smoking; microvesicles; monocytes
资金
- National Institutes of Health [HL73898]
- American Heart Association
- Temple University Department of Medicine
Objective-To investigate whether exposure of human monocytes/macrophages to tobacco smoke induces their release of membrane microvesicles (MVs) that carry tissue factor (TF) released from cells, whether smoke-induced MVs are procoagulant, and what cellular processes might be responsible for their production. Methods and Results-We found that exposure of human THP-1 monocytes and primary human monocyte-derived macrophages to 3.75% tobacco smoke extract (TSE) significantly increased their total and TF-positive MV generation. More importantly, MVs released from TSE-treated human monocytes/macrophages exhibited 3 to 4 times the procoagulant activity of control MVs, as assessed by TF-dependent generation of factor Xa. Exposure to TSE increased TF mRNA and protein expression and cell surface TF display by both THP-1 monocytes and primary human monocyte-derived macrophages. In addition, TSE exposure caused activation of C-Jun-N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK) mitogen-activated protein kinases (MAPK), and apoptosis (a major mechanism for MV generation). Treatment of THP-1 cells with inhibitors of ERK, MAP kinase kinase (MEK), Ras, or caspase 3, but not p38 or JNK, significantly blunted TSE-induced apoptosis and MV generation. Surprisingly, neither ERK nor caspase 3 inhibition altered the induction of cell surface TF display by TSE, indicating an effect solely on MV release. Inhibition of ERK or caspase 3 essentially abolished TSE-induced generation of procoagulant MVs from THP-1 monocytes. Conclusion-Tobacco smoke exposure of human monocytes/macrophages induces cell surface TF display, apoptosis, and ERK- and caspase 3-dependent generation of biologically active procoagulant MVs. These processes may be novel contributors to the pathological hypercoagulability of active and secondhand smokers. (Arterioscler Thromb Vasc Biol. 2010; 30: 1818-1824.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据