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


CONCLUSIONS
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.
Kaminsky
D A
DA
Division of Pulmonary Disease and Critical Care Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Mitchell
J
J
Carroll
N
N
James
A
A
Soultanakis
R
R
Janssen
Y
Y
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005609:Free Radicals; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D009569:Nitric Oxide / Q000378:metabolism*; D017672:Nitrogen Compounds; D013224:Status Asthmaticus / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000302:isolation & purification
D005609:Free Radicals; D017672:Nitrogen Compounds; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine