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


Xiong, Y and Karupiah, G and Hogan, SP and Foster, PS and Ramsay, AJ, Inhibition of allergic airway inflammation in mice lacking nitric oxide synthase 2, Journal of Immunology, 162, (1) pp. 445-452. ISSN 0022-1767 (1999) [Refereed Article]

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Copyright 1999 The American Association of Immunologists

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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 5560% 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.

Item Details

Item Type:Refereed Article
Keywords:Lung allergy; nitric oxide
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Innate immunity
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:142839
Year Published:1999
Web of Science® Times Cited:120
Deposited By:Medicine
Deposited On:2021-02-12
Last Modified:2021-11-16

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