Modulation of Inflammatory Process in COPD Airways

活性氮类物质（RNS）包括过氧亚硝酸根和二氧化氮，它们是由一氧化氮（NO）与超氧阴离子反应和过氧化物酶依赖性机制形成的，具有强烈的炎症作用。因此，这些分子可能会增加，并在炎症性气道疾病中发挥作用。在本研究中，我们定量RNS使用硝基酪氨酸和诱导型一氧化氮合酶（iNOS）的气道炎症细胞的诱导痰技术，以及呼出的NO浓度在慢性阻塞性肺疾病（COPD），哮喘和健康受试者（HS）的免疫染色。在气道炎症细胞中观察到的iNOS免疫反应性在COPD和哮喘中显著且相似地高于HS，尽管呼出气NO水平在哮喘中升高，但在COPD和HS中不升高。炎症细胞中的硝基酪氨酸免疫反应在COPD中明显，在哮喘中程度较轻，但在HS中不明显。COPD组1秒用力呼气容积百分比预测值与硝基酪氨酸生成量呈显著负相关，而哮喘组和HS组无相关性。这些结果表明：1）RNS可能参与了COPD气道炎症和阻塞过程的病理生物学过程; 2）气道中产生的NO可能通过iNOS与超氧阴离子和/或过氧化物酶依赖性机制反应而被消耗。

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.