Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease.
BACKGROUND
Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis.


OBJECTIVE
To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers).


METHODS
The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile.


RESULTS
Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1).


CONCLUSIONS
These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.
Ricciardolo
Fabio L M
FL
Unit of Respiratory Disease, Istituto di Ricovero e Cura a Carattere Scientifico Gaslini Institute, Genoa, Italy.
Caramori
Gaetano
G
Ito
Kazuhiro
K
Capelli
Armando
A
Brun
Paola
P
Abatangelo
Giovanni
G
Papi
Alberto
A
Chung
Kian Fan
KF
Adcock
Ian
I
Barnes
Peter J
PJ
Donner
Claudio F
CF
Rossi
Andrea
A
Di Stefano
Antonino
A
D000368:Aged; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001991:Bronchitis / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012907:Smoking; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014797:Vital Capacity; D014969:Xanthine Oxidase / Q000378:metabolism
D026361:Reactive Nitrogen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014969:Xanthine Oxidase