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

Abstract

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.

Enzymatic study of Waldeyer’s ring lymphoid tissue: Activity of alkaline and acid phosphatase in palatinal tonsils and adenoids in children with recurrent infection of the ring

“…The mechanisam of chronic tonsillitis is not yet clear. Nitric-oxide and its toxic metabolities are assumed as factors in chronic tonsillitis development (2). On the other hand enzyme arginase is in some relation with tonsillar hypertrophy (3).…”

“…The enzymatic studies point to relation of enzymes such superoxide dismutase, nitric oxide synthase and arginase in chronic tonsillitis and tonsillar hypertrophy (1)(2)(3).…”

Exhaled Nitric Oxide Levels in Children with Chronic Adenotonsillar Disease

“…It has recently been suggested that the NO pathway may be involved in the pathogenesis of chronic adenotonsillar disease on the basis of the finding of higher eNO levels in a small group of adults with recurrent tonsillar infections (11), and their normalization in the same patients after tonsillectomy (7). In addition, the enhanced immunolocalisation of iNOS and the metabolites of NO-pathway 3-nitrotyrosine (a footprint of the highly reactive peroxynitritre induced by a NO reaction to reactive oxygen species) has been found in specimens of recurrently inflamed tonsils taken from adults (9). With regard to children, who are the most affected by chronic adenotonsillar disease, Unal et al (10) reported increased venous blood levels of iNOS and arginase (a precursor of NO synthesis) in 22 children with chronic adenotonsillar hypertrophy, without mentioning infections.…”

“…It has been suggested that the NO pathway may play a role in chronic tonsillar disease (7,(9)(10)(11) as Kasperska-Zajac et al (11) found increased exhaled NO (eNO) levels in 32 adults with recurrent tonsillitis, and have recently reported a significant post-tonsillectomy reduction in eNO levels to values that were not different from those of healthy controls (7). Furthermore, there have been sporadic reports (9)(10) of an increase in the expression of inducible NO synthase (iNOS, one of the enzymatic forms involved in NO production) and the molecules involved in the NO pathway in the tonsils of adults with recurrent inflammation, as well as in venous blood samples taken from children with chronic adenotonsillar hypertrophy.…”

The presence of biofilm-producing bacteria on tonsils is associated with increased exhaled nitric oxide levels: preliminary data in children who experience recurrent exacerbations of chronic tonsillitis

“…Some authors have investigated the possible involvement of nitric oxide, 7 – 9 a highly reactive biological mediator naturally released by human airways that can be considered a marker of airway inflammation 10 . However, the findings of such studies are conflicting.…”