BACKGROUND: Recent evidence has shown that nitric oxide (NO) levels are increased 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 parenchyma of subjects with asthma who died of status asthmaticus or other nonrespiratory causes. METHODS: Lung tissue specimens were obtained from 5 patients who died of status asthmaticus, 2 asthmatic patients who died of nonrespiratory causes, and 6 nonasthmatic control subjects who died of nonrespiratory causes. Lung sections were stained for immunofluorescence with use of an antinitrotyrosine antibody, followed by a indiocarbocyanine (Cy5, Jackson Immunochemicals, Westgrove, Pa)-conjugated secondary antibody. RESULTS: Nonasthmatic lungs showed little or no nitrotyrosine staining, whereas asthmatic lungs demonstrated significantly more staining of nitrotyrosine residues distributed in both the airways and lung parenchyma. CONCLUSION: This study demonstrates the presence of nitrotyrosine, and hence evidence of formation of nitrating species, in the airways and lung parenchyma of patients with asthma who died of status asthmaticus or other nonrespiratory 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.
BACKGROUND: Recent evidence has shown that nitric oxide (NO) levels are increased 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 parenchyma of subjects with asthma who died of status asthmaticus or other nonrespiratory causes. METHODS: Lung tissue specimens were obtained from 5 patients who died of status asthmaticus, 2 asthmatic patients who died of nonrespiratory causes, and 6 nonasthmatic control subjects who died of nonrespiratory causes. Lung sections were stained for immunofluorescence with use of an antinitrotyrosine antibody, followed by a indiocarbocyanine (Cy5, Jackson Immunochemicals, Westgrove, Pa)-conjugated secondary antibody. RESULTS: Nonasthmatic lungs showed little or no nitrotyrosine staining, whereas asthmatic lungs demonstrated significantly more staining of nitrotyrosine residues distributed in both the airways and lung parenchyma. CONCLUSION: This study demonstrates the presence of nitrotyrosine, and hence evidence of formation of nitrating species, in the airways and lung parenchyma of patients with asthma who died of status asthmaticus or other nonrespiratory 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.
Authors: R A Dweik; S A Comhair; B Gaston; F B Thunnissen; C Farver; M J Thomassen; M Kavuru; J Hammel; H M Abu-Soud; S C Erzurum Journal: Proc Natl Acad Sci U S A Date: 2001-02-20 Impact factor: 11.205
Authors: Rebecca L Persinger; Matthew E Poynter; Karna Ckless; Yvonne M W Janssen-Heininger Journal: Mol Cell Biochem Date: 2002 May-Jun Impact factor: 3.396
Authors: Suzy A A Comhair; Weiling Xu; Sudakshina Ghosh; Frederik B J M Thunnissen; Alexandru Almasan; William J Calhoun; Allison J Janocha; Lemin Zheng; Stanley L Hazen; Serpil C Erzurum Journal: Am J Pathol Date: 2005-03 Impact factor: 4.307
Authors: Karina Ckless; Anniek Lampert; Jessica Reiss; David Kasahara; Matthew E Poynter; Charles G Irvin; Lennart K A Lundblad; Ryan Norton; Albert van der Vliet; Yvonne M W Janssen-Heininger Journal: J Immunol Date: 2008-09-15 Impact factor: 5.422