3-nitrotyrosine and Rhinitis--Allergic--Perennial

Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Inducible NO synthase in the nasal mucosa is upregulated in perennial allergic rhinitis, and nasal NO is reduced after treatment with topical corticosteroids. A previous study has suggested that there is a significant correlation between exhaled NO and sputum eosinophils in patients with asthma.. We investigated the ability of intranasal administration of eotaxin, a potent chemoattractant for eosinophils, to induce eosinophil accumulation and the relationship between eosinophil recruitment in the nasal mucosa and nasal NO production in patients with allergic rhinitis.. Nine patients with allergic rhinitis were studied. Eotaxin or diluent was delivered intranasally in patients by using a metered spray pump. Nasal NO, symptom scores, and the influx of inflammatory cells in nasal lavage fluid were assessed before and after the challenge. Immunoreactivity for inducible NO synthase and nitrotyrosine was evaluated in nasal lavage cells.. Eotaxin induced a significant influx of eosinophils (P <.05) with mild symptoms of rhinitis. There was neither significant migration of lymphocytes, basophils, and macrophages into nasal lavage fluid nor a shedding of nasal epithelial cells after eotaxin challenge. Nasal NO was increased significantly (P <.05) 8 hours after eotaxin challenge compared with diluent challenge. Nitrotyrosine immunoreactivity was moderately elevated in nasal epithelial cells after the challenge.. We have shown that eotaxin causes chemotaxis of eosinophils with a clinically symptomatic inflammatory response in the nasal mucosa and that eosinophil recruitment accompanies an increase in nasal NO, contributing to oxidative stress.

Topics: Administration, Intranasal; Adult; Chemokine CCL11; Chemokines, CC; Cytokines; Dose-Response Relationship, Drug; Eosinophils; Female; Humans; Male; Nasal Mucosa; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rhinitis, Allergic, Perennial; Therapeutic Irrigation; Tyrosine

Since nitric oxide (NO) can be involved in multiple physiological and pathological functions, we evaluated its possible involvement and that of peroxynitrite in the pathogenesis of rhinitis. Inferior nasal turbinates were obtained from allergic rhinitis and nonallergic rhinitis patients during corrective nasal surgery. The expressions of the inducible form of nitric oxide synthase (iNOS) and the production of peroxynitrite and its metabolite 3-nitrotyrosine were examined by immunohistochemistry in consecutive tissue sections. Each section (or tissue compartment) was given a score of 0-4 according to the labeling intensity seen, with the highest number representing the highest labeling intensity. The results showed that iNOS expression was present mainly in the mucosal epithelium, vascular endothelium, and submucosal glands. A significant difference was only observed in the labeling scores of glandular tissues of the allergic group, which had a higher iNOS labeling score. We also found that sections with a higher iNOS level did not necessarily exhibit a higher 3-nitrotyrosine labeling intensity. These data suggest that iNOS-derived NO may have a role in the pathophysiology of rhinitis, especially the glandular function of allergic nasal mucosa. Moreover, our findings suggest that the production of peroxynitrite in rhinitis patients is not dependent on the level of iNOS alone.

Topics: Adolescent; Adult; Enzyme Induction; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nasal Mucosa; Nitrates; Nitric Oxide Synthase; Rhinitis; Rhinitis, Allergic, Perennial; Turbinates; Tyrosine

The nose contributes the large amount of nitric oxide (NO) to exhaled air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO-) by reacting with superoxide (O2-). ONOO attacks tyrosine residues to form nitrotyrosine.. The aim of this study was to examine the pathophysiological role of NO in nasal mucosa in patients with perennial nasal allergy.. We measured nitrite and nitrate (NO2-/NO3-) and 3',5'-guanosine monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin concentration in nasal mucosa as an indicator of blood volume in the patients and healthy volunteers. The deleterious role of NO was also investigated by measuring nitrotyrosine in nasal mucosa.. The NO2-/NO3- concentration in the nasal lavage fluid was 39.5+/-2.8 microM in healthy volunteers (n=40), 42.4+/-3.0 microM in patients with mild allergy (mild group, n=32), and 88.7+/-6.6 microM in patients with severe allergy (severe group, n=61). In the patients whose symptoms were improved with treatment, NO2-/NO3- levels decreased to 45.7+/-10.4 microM. The concentration of cyclic GMP in nasal lavage fluid was higher in the severe group than in the healthy volunteers. The mucosal haemoglobin index was 88+/-4 in the healthy volunteers, 67+/-4 in the mild group, and 53+/-2 in the severe group. The formation of nitrotyrosine was expressed 0.58+/-10% to total tyrosine in the severe group (n=11), but was not found in non-allergy patients (n=9).. The production of NO was increased in patients with perennial nasal allergy, but the blood flow in the nasal mucosa of patients was reduced. Nitrotyrosine formation suggests that there is a process of ONOO(-)-induced damage in mucosa of patients with the perennial nasal allergy and this damage may limit the dilatation of blood vessels, despite the presence of excessive NO.

Topics: Adult; Cyclic GMP; Hemoglobins; Humans; Nasal Lavage Fluid; Nasal Mucosa; Nitrates; Nitric Oxide; Nitrites; Rhinitis, Allergic, Perennial; Tyrosine