Particulate matter-induced lung inflammation increases systemic levels of PAI-1 and activates coagulation through distinct mechanisms.
Particulate matter-induced lung inflammation increases systemic levels of PAI-1 and activates coagulation through distinct mechanisms.
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DOI：
10.1371/journal.pone.0018525
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发表时间：
2011-04-11
期刊：
影响因子：
3.7
通讯作者：
Mutlu GM
中科院分区：
文献类型：
--
作者：
Budinger GR;McKell JL;Urich D;Foiles N;Weiss I;Chiarella SE;Gonzalez A;Soberanes S;Ghio AJ;Nigdelioglu R;Mutlu EA;Radigan KA;Green D;Kwaan HC;Mutlu GM
人群暴露于环境颗粒物(PM)空气污染对缺血性心血管事件的死亡率有很大影响。我们报道，气管内滴注PM的小鼠会出现血栓前状态，需要肺泡巨噬细胞释放IL-6。我们试图确定小鼠暴露在PM中是否通过类似或不同的机制增加PAI-1的水平，PAI-1是溶栓的主要调节因子。成年、雄性C57BL/6和IL-6基因敲除(IL-6−/−)小鼠暴露于浓度小于2.5µm的环境颗粒物(CAPS)或过滤空气中，每天8小时，连续3天，或通过气管内滴注城市颗粒物或PBS，24小时后进行检查。暴露于CAPS或城市PM可导致肺和全身的IL-6依赖的凝血激活。与过滤空气或PBS对照组相比，接受CAPS或PM处理的小鼠肺和脂肪组织中PAI-1mRNA和蛋白水平更高。PAI-1在野生型和IL-6−/−小鼠中的增加相似，但在接受肿瘤坏死因子-α抑制剂依那西普治疗的小鼠中没有增加。依那西普治疗不能阻止PM诱导的血栓形成趋势。暴露于吸入PM的小鼠表现出依赖于肿瘤坏死因子-α的PAI1增加和依赖于IL-6的凝血激活。这些结果表明，PM诱导的肺部炎症与血栓前状态的发展有多种机制联系。
Exposure of human populations to ambient particulate matter (PM) air pollution significantly contributes to the mortality attributable to ischemic cardiovascular events. We reported that mice treated with intratracheally instilled PM develop a prothrombotic state that requires the release of IL-6 by alveolar macrophages. We sought to determine whether exposure of mice to PM increases the levels of PAI-1, a major regulator of thrombolysis, via a similar or distinct mechanism. Adult, male C57BL/6 and IL-6 knock out (IL-6−/−) mice were exposed to either concentrated ambient PM less than 2.5 µm (CAPs) or filtered air 8 hours daily for 3 days or were exposed to either urban particulate matter or PBS via intratracheal instillation and examined 24 hours later. Exposure to CAPs or urban PM resulted in the IL-6 dependent activation of coagulation in the lung and systemically. PAI-1 mRNA and protein levels were higher in the lung and adipose tissue of mice treated with CAPs or PM compared with filtered air or PBS controls. The increase in PAI-1 was similar in wild-type and IL-6−/− mice but was absent in mice treated with etanercept, a TNF-α inhibitor. Treatment with etanercept did not prevent the PM-induced tendency toward thrombus formation. Mice exposed to inhaled PM exhibited a TNF-α-dependent increase in PAI-1 and an IL-6-dependent activation of coagulation. These results suggest that multiple mechanisms link PM-induced lung inflammation with the development of a prothrombotic state.
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DOI：
10.1152/ajplung.00372.2007
发表时间：
2008-05-01
影响因子：
4.9
作者：
Bastarache, Julie A.;Wang, Ling;Ware, Lorraine B.
通讯作者：
Ware, Lorraine B.
影响因子：
13.6
作者：
Huggins, FE;Huffman, GP;Robertson, JD
通讯作者：
Robertson, JD
DOI：
10.1164/ajrccm.163.1.9909034
发表时间：
2001-01-01
影响因子：
24.7
作者：
Matute-Bello, G;Frevert, CW;Martin, TR
通讯作者：
Martin, TR
影响因子：
3.1
作者：
Cesari M;Pahor M;Incalzi RA
通讯作者：
Incalzi RA
DOI：
10.1164/rccm.200603-312oc
发表时间：
2007-03-15
影响因子：
24.7
作者：
Bellmeyer, Amy;Martino, Janice M.;Mutlu, Gokhan M.
通讯作者：
Mutlu, Gokhan M.