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

Am J Respir Crit Care Med. 2000 Jun;161(6):2035-42. doi: 10.1164/ajrccm.161.6.9907001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bronchiolitis Obliterans / diagnosis
  • Bronchiolitis Obliterans / immunology*
  • Bronchiolitis Obliterans / pathology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chromatography, High Pressure Liquid
  • Female
  • Forced Expiratory Volume / physiology
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Humans
  • Lung / immunology
  • Lung / pathology
  • Lung Transplantation / immunology*
  • Lung Transplantation / pathology
  • Male
  • Nitrates / metabolism*
  • Nitrites / metabolism*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / immunology*
  • Prognosis
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Nitrates
  • Nitrites
  • 3-nitrotyrosine
  • Tyrosine
  • 3-chlorotyrosine