Apocynin and 1400 W prevents airway hyperresponsiveness during allergic reactions in mice.
1. The contribution of reactive nitrogen species to the development of airway hyperresponsiveness in a mouse model of allergic inflammation was investigated by the use of selective inhibitors of nitric oxide and superoxide formation. 2. Sensitized mice, repeatedly challenged with ovalbumin showed a significant (P<0.001, n=9) increase in airway responsiveness measured using whole body plethysmography. This hyperresponsiveness was accompanied by an influx of eosinophils into the airway lumen and increased levels of ovalbumin-specific serum IgE. 3. Treatment of mice with the iNOS inhibitor 1400 W or the NADPH-oxidase inhibitor apocynin did not significantly alter cellular influx into the airway lumen nor serum ovalbumin specific IgE. In contrast, apocynin as well as 1400 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 eosinophils. Remarkably, treatment with apocynin or 1400 W did not alter 3-nitrotyrosine staining. 4. These data suggest that the development of airway hyperresponsiveness during the airway inflammation upon ovalbumin challenge is dependent on the release of both superoxide and nitric oxide and is therefore likely to be dependent on reactive nitrogen species. This mechanism, however, is not reflected by 3-nitrotyrosine formation in the airways.
Muijsers
R B
RB
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
van Ark
I
I
Folkerts
G
G
Koster
A S
AS
van Oosterhout
A J
AJ
Postma
D S
DS
Nijkamp
F P
FP
D000098:Acetophenones / Q000494:pharmacology*; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010047:Ovalbumin / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000098:Acetophenones; D000578:Amidines; D000975:Antioxidants; D001596:Benzylamines; D004791:Enzyme Inhibitors; D015848:Interleukin-5; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D015847:Interleukin-4; C002744:3-nitrotyrosine; D007073:Immunoglobulin E; D014443:Tyrosine; D007371:Interferon-gamma; D010047:Ovalbumin; C056165:acetovanillone; D019001:Nitric Oxide Synthase