INCREASED EXPRESSION OF AN INDUCIBLE ISOFORM OF NITRIC-OXIDE SYNTHASEAND THE FORMATION OF PEROXYNITRITE IN COLONIC MUCOSA OF PATIENTS WITHACTIVE ULCERATIVE-COLITIS

Background-Increased production of reactive metabolites of oxygen and nitrogen bras been implicated in chronic inflammation of the gut. The object of this study was to examine the magnitude and location of nitr ic oxide synthase (NOS) activity and peroxynitrite formation in the co lonic mucosa of patients with ulcerative colitis In relation to the de gree of inflammation. Subjects-Thirty three patients with active ulcer ative colitis (17 with mild or moderate inflammation, 16 with severe i nflammation):. Methods-Inducible NOS activity was determined in the co lonic mucosa by measuring the conversion of L-arginine to citrulline i n the absence of calcium. The localisation of NOS and nitrotyrosine im munoreactivity was assessed immuno-histochemically using the labelled streptavidin biotin method. Results-Inducible NOS activity increased i n parallell with the degree of inflammation of the mucosa. Expression of inducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed by nitrotyrosine staining was frequently observed in the lamina propria of actively inflamed mucosa. Conclusions-Nitric oxide and peroxynitrit e formation may play an important role in causing irreversible cellula r injury to the colonic mucosa in patients with active ulcerative coli tis.