Nemmar Abderrahim, Nemery Benoit, Hoet Peter H M, Vermylen Jos, Hoylaerts Marc F
Laboratory of Pneumology (Lung Toxicity) and Center for Molecular and Vascular Biology, K. U. Leuven, Leuven, Belgium.
Am J Respir Crit Care Med. 2003 Dec 1;168(11):1366-72. doi: 10.1164/rccm.200306-801OC. Epub 2003 Sep 11.
Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEPs) are prothrombotic. Here, we investigated the time course and the mechanisms. At 1, 6, and 24 hours after instillation of 50 microg DEPs per hamster, the mean size of in vivo-induced and quantified venous thrombosis was increased by 480%, 770%, and 460%, respectively. Platelets activation in blood was confirmed by a shortened closure time in the platelet function analyzer (PFA-100). In bronchoalveolar lavage, neutrophils and histamine levels were increased at all time points. In plasma, histamine was increased at 6 and 24 hours but not at 1 and 3 hours. Pretreatment with a histamine H1-receptor antagonist (diphenhydramine, 30 mg/kg intraperitoneally) abolished the DEP-induced neutrophil influx in bronchoalveolar lavage at all time points. However, diphenhydramine pretreatment did not affect DEP-induced thrombosis or platelet activation at 1 hour, whereas both were markedly reduced at 6 and 24 hours. In conclusion, pulmonary inflammation and peripheral thrombosis are correlated at 6 and 24 hours, but at 1 hour, the prothrombotic effects do not appear to result from pulmonary inflammation but possibly from the blood penetration of DEP-associated components or by DEP particles themselves.
短期的空气污染颗粒物增加与心血管事件发生率上升有关。此前，我们发现经气管内注入的柴油废气颗粒（DEP）具有促血栓形成作用。在此，我们研究了其时间进程及机制。每只仓鼠经气管内注入50微克DEP后1小时、6小时和24小时，体内诱导并定量的静脉血栓平均大小分别增加了480%、770%和460%。血小板功能分析仪（PFA - 100）检测显示血液中血小板活化，其闭合时间缩短。支气管肺泡灌洗中，所有时间点中性粒细胞和组胺水平均升高。血浆中，组胺在6小时和24小时升高，但在1小时和3小时未升高。用组胺H1受体拮抗剂（苯海拉明，30毫克/千克腹腔注射）预处理可消除DEP在所有时间点诱导的支气管肺泡灌洗中性粒细胞流入。然而，苯海拉明预处理在1小时时不影响DEP诱导的血栓形成或血小板活化，而在6小时和24小时时两者均显著降低。总之，肺部炎症与外周血栓形成在6小时和24小时相关，但在1小时时，促血栓形成作用似乎并非由肺部炎症引起，而是可能由DEP相关成分的血液渗透或DEP颗粒本身导致。
