Nitric oxide and protein nitration in the cystic fibrosis airway.
Cystic fibrosis (CF), characterized by chronic airway infection and inflammation, ultimately leads to respiratory failure. Exhaled nitric oxide (NO), elevated in most inflammatory airway diseases, is decreased in CF, suggesting either decreased production or accelerated metabolism of NO. The present studies performed on two groups of CF patients provide further support for a disordered NO airway metabolism in CF respiratory tract disease. Despite confirmation of subnormal NOS2 in the CF airway epithelium, alternative isoforms NOS1 and NOS3 were present, and inflammatory cells in the CF airway expressed abundant NOS2. Increased immunohistochemical staining for nitrotyrosine was demonstrated in lung tissues from patients with CF as compared to control. To our knowledge, this is the first report localizing nitrotyrosine in diseased CF lung tissue. While the relative NOS2 deficiency in CF respiratory tract epithelium may contribute to the lower expired NO levels, these results suggest that increased metabolism of NO is also present in advanced CF lung disease. The significance of altered NO metabolism and protein nitration in CF remains to be fully elucidated.
Morrissey
Brian M
BM
Division of Pulmonary and Critical Care Medicine, University of California, Davis and Department of Pulmonary Sciences and Critical Care Medicine, Sacramento, CA 95817, USA. bmmorrissey@ucdavis.edu
Schilling
Kevin
K
Weil
John V
JV
Silkoff
Philip E
PE
Rodman
David M
DM
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D012016:Reference Values; D015656:Respiratory Mechanics / Q000502:physiology*; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*
D009566:Nitrates; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II