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Effects of diesel exhaust particles on cardiorespiratory health

柴油机尾气颗粒物对心肺健康的影响

基本信息

批准号：
13480173
负责人：
TAKANO Hirohisa
金额：
$ 4.1万
依托单位：
National Institute for Environmental Studies
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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).

流行病学研究表明，颗粒物空气污染对心肺健康产生急性和严重的不利影响，特别是对易受细菌感染的易感人群。我们确定了柴油废气颗粒（DEP）对小鼠细菌内毒素相关肺损伤的影响，DEP是颗粒污染物的主要参与者。气管内滴注DEP可协同增强革兰氏阴性菌内毒素引起的肺损伤，其特征为中性粒细胞隔离、间质水肿和肺泡出血。在内毒素存在下，DEP进一步激活肺内NF-κ B p65亚基核易位，增加肺内ICAM-1、IL-1 β、巨噬细胞趋化蛋白-1、KC、巨噬细胞炎症蛋白-1 α和toll样受体的表达。单独给药DEP增加了toll样受体4的表达和NF-κ b p50亚基的核定位，这些结果首次提供了DEP增强与细菌内毒素相关的中性粒细胞肺炎症的实验证据。这种增强可能是通过诱导促炎分子介导的，可能是通过toll样受体的表达和NF-κ B含有p65的二聚体(s)如p65/p50的激活（文献5）。此外，我们已经证明DEP或DE可能通过增强IL-5和EOTAXIN的表达来增强与屋尘螨过敏原相关的气道炎症（文献6,9）。在另一系列实验中，我们已经证明DE可以增强即时和晚期气道反应以及粘液分泌（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（文献2,3）。最后，我们已经证明DE中的二氧化氮可以增加动脉粥样硬化代谢并发症，特别是在肥胖受试者中（提交）。