Modulation of Inflammatory Process in COPD Airways

慢性阻塞性肺病气道炎症过程的调节

基本信息

批准号：
12470132
负责人：
ICHINOSE Masakazu
金额：
$ 2.88万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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.

反应性氮种（RN），包括过氧亚硝酸盐和二氧化氮，它们是在氮氧化物（NO）与超氧化物阴离子和过氧化物酶依赖性机制的反应中形成的，具有有效的炎症作用。因此，这些分子可能会增加并在炎症性气道疾病中起作用。在本研究中，我们使用硝基酪氨酸的免疫染色和可诱导的NO合酶（INOS）在气道炎性细胞中量化了RN，并通过诱导的痰液技术获得的气道炎症细胞以及慢性阻塞性肺病（COPD），哮喘和健康的子季的慢性阻塞性肺部疾病（COPD）中的无浓度（HS）。与HS相比，在气道炎症细胞中观察到的iNOS免疫反应性显着且类似地更高，尽管呼出的哮喘中没有呼出的无水平升高，但在COPD和HS中没有升高。炎症细胞中的亚硝基酪氨酸免疫反应性在COPD中是明显的，在哮喘中的程度较小，而在HS中则不明显。在一秒钟内强制呼气量的预测值的百分比与COPD中的硝基酪氨酸形成的量之间存在显着的负相关性，而在哮喘和HS中则不显着。这些结果表明，1）RN可能参与COPD气道炎症和阻塞过程的病理生物学，2）在气道中没有产生的（大概是通过Inos）与超级氧化物和/或过氧化物酶 - 或过氧化物酶 - 依赖机制。