Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 2035-2042

Protein Nitration, Metabolites of Reactive Nitrogen Species, and Inflammation in Lung Allografts

JOÃO A. DE ANDRADE, JOHN P. CROW, LILIANA VIERA, C. BRUCE ALEXANDER, K. RANDALL YOUNG, DAVID C. MCGIFFIN, GEORGE L. ZORN, SHA ZHU, SADIS MATALON, and ROBERT M. JACKSON

Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, and Birmingham Department of Veterans Affairs Medical Center, Birmingham, Alabama

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 (NO₃), and nitrate (NO₂) in bronchoalveolar lavage fluid (BALF) and total nitrite (NO₂ + NO₃) 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 × 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 × 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 (NO₂ + NO₃) in BALF of the patients: 3.3 (1.9-5.1) µM significantly exceeded that in control subjects: 1.3 (0.8-1.3) µM; p = 0.0133. Serum nitrite also was significantly higher in patients: 37 (26-55) µM than control subjects: 19 () µM; 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.

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