Nemmar Abderrahim, Hoet Peter H M, Vermylen Jos, Nemery Benoit, Hoylaerts Marc F
Laboratory of Pneumology, Lung Toxicology Unit, Katholieke Universiteit Leuven, Leuven, Belgium.
Circulation. 2004 Sep 21;110(12):1670-7. doi: 10.1161/01.CIR.0000142053.13921.21. Epub 2004 Sep 13.
Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).
We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 microg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy. Lung inflammation and histamine analysis in bronchoalveolar lavage (BAL) and plasma were performed after pretreatment with dexamethasone (DEX) or sodium cromoglycate (SC). DEP induced airway inflammation and histamine release in BAL and in plasma, and increased thrombosis, without elevating plasma von Willebrand factor (vWF) levels. The IT instillation of 400-nm positively charged polystyrene particles (500 microg/hamster), serving as particles that do not penetrate into the circulation, equally produced airway inflammation, histamine release, and enhanced thrombosis. Histamine in plasma resulted from basophil activation. Intraperitoneal (IP) pretreatment with DEX (5 mg/kg) abolished the DEP-induced histamine increase in BAL and plasma and abrogated airway inflammation and thrombogenicity. The IT pretreatment with DEX (0.5 mg/kg) showed a partial but parallel inhibition of all of these parameters. Pretreatment with SC (40 mg/kg, IP) strongly inhibited airway inflammation, thrombogenicity, and histamine release.
Our results are compatible with the triggering of mast cell degranulation and histamine release by DEP. Histamine plays an initial central role in airway inflammation, further release of histamine by circulating basophils, and peripheral thrombotic events. Antiinflammatory pretreatment can abrogate the peripheral thrombogenicity by preventing histamine release from mast cells.
空气污染颗粒与心血管疾病及心肌梗死（MI）相关。
我们研究了气管内（IT）滴注柴油废气颗粒（DEP；50微克/仓鼠）24小时后气道炎症与血栓形成之间的关系。通过内皮损伤在股静脉诱导轻度血栓形成，并通过在线视频显微镜研究气道炎症对血栓形成倾向的影响。在用地塞米松（DEX）或色甘酸钠（SC）预处理后，对支气管肺泡灌洗（BAL）液和血浆中的肺炎症及组胺进行分析。DEP诱导气道炎症以及BAL液和血浆中的组胺释放，并增加血栓形成，而不提高血浆血管性血友病因子（vWF）水平。滴注400纳米带正电荷的聚苯乙烯颗粒（500微克/仓鼠），作为不进入循环的颗粒，同样产生气道炎症、组胺释放及增强的血栓形成。血浆中的组胺源于嗜碱性粒细胞活化。腹腔内（IP）用地塞米松（5毫克/千克）预处理可消除DEP诱导的BAL液和血浆中组胺增加，并消除气道炎症和血栓形成倾向。IT用地塞米松（0.5毫克/千克）预处理对所有这些参数表现出部分但平行的抑制作用。用SC（40毫克/千克，IP）预处理可强烈抑制气道炎症、血栓形成倾向及组胺释放。
我们的结果与DEP触发肥大细胞脱颗粒和组胺释放相符。组胺在气道炎症、循环嗜碱性粒细胞进一步释放组胺及外周血栓形成事件中起初始核心作用。抗炎预处理可通过防止组胺从肥大细胞释放来消除外周血栓形成倾向。
