Increase in Reactive Nitrogen Species Production in Chronic Obstructive Pulmonary Disease Airways

Abstract

Peroxynitrite, nitrogen dioxide, and other reactive nitrogen species (RNS) that are formed in the reaction of nitric oxide (NO) with superoxide anion, and in peroxidase-dependent mechanisms, have a potent inflammatory action. These molecules may therefore increase in number and have a role in inflammatory airway diseases. In the present study, we quantified RNS using immunostaining of nitrotyrosine and inducible NO synthase (iNOS) in airway inflammatory cells obtained by the induced sputum technique, and also quantified the exhaled NO concentration in subjects with chronic obstructive pulmonary disease (COPD), subjects with asthma, and healthy subjects (HS). Immunoreactivity for iNOS observed in the airway inflammatory cells was significantly and similarly higher in subjects with COPD and asthma than in HS, although exhaled NO levels were increased only in subjects with asthma. Inflammatory cells showed obvious nitrotyrosine immunoreactivity in subjects with COPD and to a lesser extent in those with asthma, but not in HS. There was a significant negative correlation between the percent predicted values of FEV(1) and the amount of nitrotyrosine formation in subjects with COPD, but not in those with asthma and HS. These results suggest that: (1) RNS may be involved in the pathobiology of the airway inflammatory and obstructive process in COPD; and (2) NO produced in the airways, presumably via iNOS, is consumed by its reaction with superoxide anion and/or peroxidase-dependent mechanisms.