COPD的发病率及死亡率在我国呈逐年上升趋势，雾霾和空气污染是诱发并加重COPD形成的重要原因。近年来的研究发现，雾霾所含的氮氧化物可通过诱导蛋白硝基化改变细胞的生物学功能。中性粒细胞是引发COPD患者炎症形成的主要原因，巨噬细胞对凋亡的中性粒细胞的清除作用，可以避免造成二次炎症反应，是抗炎治疗的关键。但是在COPD的患者中，呼吸道巨噬细胞对中性粒细胞的吞噬机能明显减弱，我们推测，雾霾诱导的蛋白质硝基化可能是改变巨噬细胞吞噬功能的主要原因。为此我们将研究：①COPD患者呼吸道巨噬细胞功能的改变与蛋白质硝基化修饰间的关系；②在动物模型中，研究蛋白质硝基化在COPD形成过程中的作用以及硝基化抑制剂对COPD的保护作用；③ 阐明蛋白质硝基化影响巨噬细胞吞噬功能的分子机制。本课题首次关注雾霾诱导的蛋白质硝基化对COPD发病的影响，为减轻雾霾对健康所造成的不利影响，防治COPD的发病提供新的思路。

Association of ambient air pollution and sever haze formation, the incidence and prevalence of COPD keep increasing in our country. In recent years, it has been recognized that the reactive nitrogen species existed in the air pollution could induce the protein nitration, which result in the functional alteration in relevant cells. Neutrophil, as a major cell type which can trigger the airway inflammaiton during the process of COPD development, could be eliminated by macrophage phagocytosis. The macrophage mediated neutrophil phagocytosis significantly reduced the chance for the development of secondary inflammatory responses, thus proved to be crucial for the maintaining of immunol homeostasis in the local tissue. In recent years, it has been found that the patients with COPD have defective macrophage phagocytosis, however the mechanism is still not known. We hypothesis that protein nitration induced by sever haze and air pollution might be the major cause contributed to the defective effect of macrophage phagocytosis, therefore in this present study, we aim to perform the following studies. 1) the relationship between the protein nitration and the defected macrophage phagocytosis in COPD patients; 2) By using the relevant animal models, we are going to investigate the effect of protein nitration for the pathological development of COPD; 3) Investigate the molecular mechanism why the protein nitration could alter the macrophage phagocytosis functions in COPD patients; This is the first study to investigate the effect of protein nitration for the pathological development of COPD, which is very important for reducing the bad influence of sever haze and air pollution to the human health, and also, our study provide a direct experimental evidence for the prevention and treatment of the disease of COPD.