Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters
Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters
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DOI：
10.1161/01.cir.0000142053.13921.21
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发表时间：
2004-09-21
期刊：
影响因子：
37.8
通讯作者：
Hoylaerts, MF
中科院分区：
文献类型：
--
作者：
Nemmar, A;Hoet, PHM;Hoylaerts, MF
背景-空气颗粒物污染与心血管疾病和心肌梗死(MI)有关。方法和结果-我们研究了气管内滴注柴油废气颗粒物(DEP；50µg/只)24小时后，呼吸道炎症和血栓形成的关系。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呼吸道炎症对血栓形成的影响。用地塞米松(DEX)或色甘酸钠(SC)预处理后，测定肺组织炎症反应及肺泡灌洗液(BAL)和血浆中的组胺含量。DEP可诱导BAL和血浆中的组胺释放和气道炎症，增加血栓形成，但不增加血浆von Willebrand因子(VWF)水平。IT注射400纳米带正电的聚苯乙烯颗粒(500杯/仓鼠)，作为不能渗透到循环中的颗粒，同样会产生呼吸道炎症、组胺释放和增强血栓形成。血浆中的组胺是嗜碱性粒细胞活化的结果。腹腔注射地塞米松(5 mg/kg)可抑制DEP诱导的BAL和血浆组胺升高，抑制气道炎症和血栓形成。地塞米松(0.5 mg/kg)对上述指标均有部分但平行的抑制作用。SC(40 mg/kg，ip)可显著抑制气道炎症、血栓形成和组胺释放。结论--我们的结果与DEP触发的肥大细胞脱颗粒和组胺释放相一致。组胺在呼吸道炎症、循环嗜碱性粒细胞进一步释放组胺以及外周血栓性事件中起主要作用。抗炎预处理可通过阻止肥大细胞释放组胺来消除外周血栓形成。
Background-Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).Methods and Results-We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 mug/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 mug/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.Conclusions-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.