Protein nitration, metabolites of reactive nitrogen species, and inflammation in lung allografts

This study investigated nitration and chlorination of epithelial lining flu id (ELF) proteins in patients (n = 29) who had undergone lung allotransplan tation. We assayed lung lavage nitrotyrosine (NT) and chlorotyrosine (CT) b y HPLC. We measured NT, nitrate (NO3-), and nitrate (NO2-) in bronchoalveol ar 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), pe rcent nitration of tyrosines (Tyr) (NT/total Tyr x 100) in BALF proteins wa s: patients, 0.01 (0.00-0.12)%; median (25th-75th% confidence interval), an d 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), ni trotyrosine (NT) was detected by ELISA in the BALF of patients: 9 (0-41) pm ol/mg pro and control subjects: 28 (26-33). Total nitrite (NO2- + NO3-) in BALF of the patients: 3.3 (1.9-5.1) mu M significantly exceeded that in con trol subjects: 1.3 (0.8-1.3) mu M; p = 0.0133. Serum nitrite also was signi ficantly higher in patients: 37 (26-55) mu M than control subjects: 19 (17- 20) mu M; p = 0.0037. Airway inflammation in transbronchial biopsies (B sco re) correlated with NT in BALF (p = 0.0369). Lung transplants have increase d airway concentrations of reactive nitrogen species (RNS) metabolites. NT, a marker of peroxynitrite (ONOO-), is related to the degree of airway infl ammation in lung transplants.