Modulation of Inflammatory Process in COPD Airways

活性氮（Reactive nitrogen species， RNS）包括过氧亚硝酸盐和二氧化氮，它们是由一氧化氮（nitrogen oxide， NO）与超氧阴离子和过氧化物酶依赖机制反应形成的，具有强大的炎症作用。因此，这些分子可能在炎症性气道疾病中增加并发挥作用。本研究采用诱导痰法获得气道炎症细胞，采用免疫染色法测定硝基酪氨酸和诱导型NO合成酶（iNOS）的RNS以及慢性阻塞性肺疾病（COPD）、哮喘和健康受试者（HS）呼出的NO浓度。与HS相比，COPD和哮喘患者气道炎症细胞iNOS免疫反应性明显升高，但哮喘患者呼出NO水平升高，而COPD和HS未见此变化。慢性阻塞性肺病患者炎症细胞中有明显的硝基酪氨酸免疫反应性，哮喘患者有较轻程度的免疫反应性，而HS无明显反应性。COPD患者1秒用力呼气量预测值与硝基酪氨酸生成量呈显著负相关，哮喘和HS患者无显著负相关。这些结果表明，1)RNS可能参与COPD气道炎症和阻塞性过程的病理生物学过程；2)气道中产生的NO（可能是通过iNOS产生的）似乎通过其与超氧阴离子和/或过氧化物酶依赖机制的反应被消耗。

Reactive nitrogen species (RNS) including peroxynitrite and nitrogen dioxide, which are formed in the reaction of nitrogen oxide (NO) with superoxide anion and peroxidase-dependent mechanisms, have a potent inflammatory action. Therefore, these molecules may increase and have a role in inflammatory airway diseases. In the present study, we quantified the RNS using immunostaining of nitrotyrosine and inducible NO synthase (iNOS) in airway inflammatory cells obtained by the induced sputum technique as well as the exhaled NO concentration in chronic obstructive pulmonary disease (COPD), asthma and healthy subjets (HS). iNOS immunoreactivity observed in the airway inflammatory cells was significantly and similarly higher in COPD and asthma compared with HS, although the exhaled NO levels were elevated in asthma but not in COPD and HS. The nitrotyrosine immunoreactivity in the inflammatory cells was obvious in COPD and to a lesser extent in asthma but not in HS. There was a significant negative correlation between the percent predicted values of forced expiratory volume in one second and the amount of nitrotyrosine formation in COPD but not in asthma and HS. These results suggest that 1)RNS may be involved in the pathobiology of the airway inflammatory and obstructive process in COPD, 2)NO produced in the airways, presumably via iNOS, seems to be consumed by its reaction with superoxide anion and/or peroxidase-dependent mechanisms.