Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma

Background: Recent evidence has shown that nitric oxide (NO) levels are inc reased in asthmatic airways. Although the role of NO in asthma is unknown, reactive metabolites of NO may lead to nitrotyrosine formation and promote airway dysfunction. Objective: The aim of this study was to determine whether nitrotyrosine, as a marker of nitrating species, could be found in the airways and lung pare nchyma of subjects with asthma who died of status asthmaticus or other nonr espiratory causes. Methods: Lung tissue specimens were obtained from 5 pati ents who died of status asthmaticus, 2 asthmatic patients who died of nonre spiratory causes, and 6 nonasthmatic control subjects who died of nonrespir atory causes. Lung sections were stained for immunofluorescence with use of an antinitrotyrosine antibody, followed by a indiocarbocyanine (Cy5, Jacks on Immunochemicals, Westgrove, Pa)-conjugated secondary antibody. Results: Nonasthmatic lungs showed little or no nitrotyrosine staining, whe reas asthmatic lungs demonstrated significantly more staining of nitrotyros ine residues distributed in both the airways and lung parenchyma. Conclusion: This study demonstrates the presence of nitrotyrosine, and henc e evidence of formation of nitrating species, in the airways and lung paren chyma of patients with asthma who died of status asthmaticus or other nonre spiratory causes, This finding supports the concept that widespread airway and parenchymal inflammation occurs in asthma, and, more specifically, that NO and its reactive metabolites may play a pathophysiologic role in asthma .