Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in recurrently inflamed, human palatine tonsils

The purpose of this study was to evaluate the possible involvement of nitric oxide and its toxic metabolite - peroxynitrite - in the pathogenesis of recurrent tonsillitis. Tonsil specimens with recurrent inflammation were obtained from patients who required tonsillectomies as surgical treatment for their conditions. The relatively normal tonsils were obtained from patients who underwent uvulo-palato-pharyngoplasty for habitual snoring or obstructive sleep apnea. The sites of inducible nitric oxide synthase (iNOS) expression in the tonsil specimens were examined with an immunohistochemical technique. The possible production of peroxynitrite was evaluated by immunolabeling of 3-nitrotyrosine (3-NT) as its biological footprint. Each section was given a score of 0 to 4 according to the labeling intensity seen, with the highest number representing the highest labeling intensity. We found that tonsils with recurrent inflammation had iNOS expression mainly in the mucosal epithelium, subepithelial regions and vascular endothelium. The parenchyma of the tonsils, where T- and B-cell clones are located, showed little iNOS immunoreactivity. The accumulation of 3-NT had a similar distribution pattern to that of iNOS expression. However, the normal tonsils showed limited iNOS expression on mucosal epithelium and rare 3-NT accumulation. Recurrently inflamed tonsils had significantly higher labeling scores for both iNOS and 3-NT compared to normal tonsils. Further, a higher iNOS score correlated with a higher 3-NT accumulation. These data suggest that iNOS expression and the formation of peroxynitrite may have an important role in the pathogenesis of recurrent tonsillitis.