Protein nitration, metabolites of reactive nitrogen species, and inflammation in lung allografts.
This study investigated nitration and chlorination of epithelial lining fluid (ELF) proteins in patients (n = 29) who had undergone lung allotransplantation. We assayed lung lavage nitrotyrosine (NT) and chlorotyrosine (CT) by HPLC. We measured NT, nitrate (NO(3)(-)), and nitrate (NO(2)(-)) in bronchoalveolar lavage fluid (BALF) and total nitrite (NO(2)(-) + NO(3)(-)) in serum of another group of lung transplant patients (n = 82). In the first group (n = 29), percent nitration of tyrosines (Tyr) (NT/total Tyr x 100) in BALF proteins was: patients, 0.01 (0.00-0.12)%; median (25th-75th% confidence interval), and control subjects 0.01 (0.00-0.02)%. CT (CT/ total Tyr x 100) occurred only in the patients' BALF: 0.01 (0. 00- 0.02)%. In the second group (n = 82), nitrotyrosine (NT) was detected by ELISA in the BALF of patients: 9 (0-41) pmol/mg pro and control subjects: 28 (26-33). Total nitrite (NO(2)(-) + NO(3)(-)) in BALF of the patients: 3.3 (1.9-5.1) microM significantly exceeded that in control subjects: 1.3 (0.8-1.3) microM; p = 0.0133. Serum nitrite also was significantly higher in patients: 37 (26-55) microM than control subjects: 19 (17-20) microM; p = 0.0037. Airway inflammation in transbronchial biopsies (B score) correlated with NT in BALF (p = 0.0369). Lung transplants have increased airway concentrations of reactive nitrogen species (RNS) metabolites. NT, a marker of peroxynitrite (ONOO(-)), is related to the degree of airway inflammation in lung transplants.
De Andrade
J A
JA
Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, 35294-0006, USA.
Crow
J P
JP
Viera
L
L
Bruce Alexander
C
C
Randall Young
K
K
McGiffin
D C
DC
Zorn
G L
GL
Zhu
S
S
Matalon
S
S
Jackson
R M
RM
D000328:Adult; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D011183:Postoperative Complications / Q000175:diagnosis / Q000276:immunology*; D011379:Prognosis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine; C087259:3-chlorotyrosine