Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease

Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in the pathogenesis of inflammatory bowel disease (IBD), NO in IBD can be either harmful or protective. NO can react with superoxide anions (O-2(.-)) , yielding the toxic oxidizing agent peroxynitrite (ONOO-). Peroxynitrite i nduces nitration of tyrosine residues (nitrotyrosine), leading to changes o f protein structure and function. The aim of this study was to identify the cellular source of inducible nitric oxide synthase (iNOS) and to localize superoxide anion-producing cells in mucosal biopsies from patients with act ive IBD, Additional studies were performed to look at nitrotyrosine formati on as a measure of peroxynitrite-mediated tissue damage, For this, antibodi es against iNOS, endothelial NOS (eNOS), and nitrotyrosine were used, ROS-p roducing cells were detected cytochemically. inflamed mucosa of patients wi th active IBD showed intense iNOS staining in the epithelial cells, iNOS co uld not be detected in non-inflamed mucosa of IBD patients and control subj ects. eNOS was present in blood vessels, without any difference in the stai ning intensity between IHD patients and control subjects. ROS-producing cel ls were increased in the lamina propria of IBD patients; a fraction of thes e cells were CD15-positive. Nitrotyrosine formation was found on ROS-positi ve cells. These results show that iNOS is induced in epithelial cells from patients with active ulcerative colitis or Crohn's disease, Nitration of pr oteins was detected only on the ROS-producing cells at some distance from t he iNOS-producing epithelial cells, These findings indicate that tissue dam age during active inflammation in IBD patients is probably more related to ROS-producing cells than to NO. One mag, speculate that NO has a protective role when during active inflammation other mucosal defence systems are imp aired, (C) 1998 John Wiley & Sons, Ltd.