University Of Tasmania

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Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2

journal contribution
posted on 2023-05-20, 21:02 authored by Xiong, Y, Gunasegaran KarupiahGunasegaran Karupiah, Hogan, SP, Foster, PS, Ramsay, AJ
We have used mice rendered deficient for nitric oxide synthase 2 (NOS2) production to study the role of inducible nitric oxide (NO) in the pathogenesis of allergic airways disease. Using a model with OVA as aeroallergen, we show that the manifestations of disease, including infiltration of inflammatory cells, particularly eosinophils, loss of structural integrity of the airway walls, microvascular leakage, pulmonary edema, and airway occlusion are markedly less severe in the NOS2 mutants than in wild-type animals. Indeed, NOS2-deficiency resulted in a 55–60% reduction in both circulatory and pulmonary eosinophil numbers following aeroallergen treatment, although eosinophil maturation or efflux from the bone marrow was not suppressed. There were no obvious differences in levels of airway hyperreactivity recorded in OVA-treated wild-type and NOS2-deficient mice. Interestingly, the suppression of allergic inflammation was accompanied by marked increases in T cell production of IFN-g but not by any obvious reduction in the secretion of either IL-4 or IL-5, nor by major changes in the IgG1 and IgE OVA-specific serum Ig profiles in the mutants. The markedly enhanced production of IFN-g in NOS22/2 mice was apparently responsible for the suppression of both eosinophilia and disease, as in vivo depletion of this factor restored allergic pathology in these animals. Our data indicate that NOS2 promotes allergic inflammation in airways via down-regulation of IFN-g activity and suggest that inhibitors of this molecule may represent a worthwhile therapeutic strategy for allergic diseases including asthma.


Publication title

Journal of Immunology








Tasmanian School of Medicine


Amer Assoc Immunologists

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814

Rights statement

Copyright 1999 The American Association of Immunologists

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  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions

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