Apocynin and 1400 W prevents airway hyperresponsiveness during allergic reactions in mice

1 The contribution of reactive nitrogen species to the development of airwa y hyperresponsiveness in a mouse model of allergic inflammation was investi gated by the use of selective inhibitors of nitric oxide and superoxide for mation. 2 Sensitized mice, repeatedly challenged with ovalbumin showed a significan t (P < 0.001, n = 9) increase in airway responsiveness measured using whole body plethysmography. This hyperresponsiveness was accompanied by an influ x of eosinophils into the airway lumen and increased levels of ovalbumin-sp ecific serum IgE. 3 Treatment of mice with the iNOS inhibitor 1400 W or the NADPH-oxidase inh ibitor apocynin did not significantly alter cellular influx into the airway lumen nor serum ovalbumin specific IgE. In contrast, apocynin as well as 1 400 W inhibited ovalbumin-induced airway hyperresponsiveness (P <0.001 and P <0.05 respectively, n=9). Furthermore, the airways of allergen challenged animals showed clear 3-nitrotyrosine staining, which was mainly located in cosinophils. Remarkably, treatment with apocynin or 1400 W did not alter 3 -nitrotyrosine staining. 4 These data suggest that the development of airway hyperresponsiveness dur ing the airway inflammation upon ovalbumin challenge is dependent on the re lease of both superoxide and nitric oxide and is therefore likely to be dep endent on reactive nitrogen species. This mechanism, however, is not reflec ted by 3-nitrotyrosine formation in the airways.