Effects of diesel exhaust particles on cardiorespiratory health

流行病学研究表明，颗粒性空气污染对心肺健康的严重不利影响，特别是对易受细菌感染的易感人群。我们测定了微粒污染物的主要参与者柴油废气颗粒物(DEP)对细菌内毒素引起的小鼠肺损伤的影响。气管内滴注DEP协同增强与革兰氏阴性细菌内毒素相关的肺损伤，其特征是中性粒细胞隔离、间质水肿和肺泡出血。在内毒素存在的情况下，DEP进一步激活了肺组织中NF-κB p65亚基的核移位，增加了肺组织中ICAM-1、IL-1β、巨噬细胞趋化蛋白-1、KC、巨噬细胞炎性蛋白-1α和Toll样受体的表达。单独给予DEP可增加肺组织Toll样受体4的表达和NF-κB p50亚单位的核定位。这些结果首次为DEP增强与细菌内毒素相关的中性粒细胞炎症提供了实验证据。这种增强作用可能是通过表达Toll样受体和激活含有p65/p50的NF-κB的p65二聚体(S)来介导的。此外，我们还发现DEP或DE可能通过增强IL-5和嗜酸性粒细胞趋化蛋白的表达而增强与屋尘螨变应原相关的气道炎症(参考文献6，9)。在另一系列实验中，我们证明DE可增强即刻和晚期呼吸道反应以及粘液分泌(参考文献1)。此外，DEP可以通过改变口服耐受性或Th1/Th2平衡来影响免疫系统(参考文献2，3)。最后，我们已经证明，DE中的二氧化氮可以增加致动脉粥样硬化的代谢并发症，特别是在肥胖的受试者(提交)。

Epidemiology studies demonstrate acute and serious adverse effects of particulate air pollution on cardiorespiratory health especially in the predisposed people susceptible to bacterial infection. We determined the effects of diesel exhaust particles (DEP), major participants in particulate pollutants, on lung injury related to bacterial endotoxin in mice. Intratracheal instillation of DEP synergistically enhanced lung injury related to endotoxin from gram-negative bacteria, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. In the presence of endotoxin, DEP further activated the nuclear translocation of p65 subunit of NF-κ B in the lung, and increased the lung expression of ICAM-1, IL-1 β , macrophage chemoattractant protein-1, KC, macrophage inflammatory protein-1 α , and Toll-like receptors. DEP given alone increased the lung expression of Toll-like receptor 4 and the nuclear localization of p50 subunit of NF-κ B. These results provide the first experimental evidence that DEP enhance neutrophilic lung inflammation related to bacterial endotoxm. The enhancement should be mediated by the induction of proinflammatory molecules likely through the expression of Toll-like receptors and the activation of p65-containing dimer(s) of NF-κ B such as p65/p50 (reference 5).Furthermore, we have shown DEP or DE enhance airway inflammation related to house dust mite allergen possibly via the enhanced expression of IL-5 and EOTAXIN (reference 6, 9). In another series of experiments, we have demonstrated that DE enhances both immediate and late airway responses as well as mucus secretion (reference 1). In addition, DEP can affect immune systems via the modification of oral tolerance or Th1/Th2 balance (reference 2, 3). Finally, we have demonstrated that nitrogen dioxide in DE can enhance atherogenic metabolic complications especially in obese subjects (submitted).