Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma
Autor: | Hartmut Grasemann, Paul L. Huang, Changaram S. Venugopal, Lester Kobzik, Kaoru Hamada, Aiping Jiao, Jeffrey M. Drazen, James A. MacLean, George T. De Sanctis, Chandri N. Yandava, Jeremy A. Scott, Sanjay Mehta, Attila J. Fabian, Walter W. Wolyniec |
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Jazyk: | angličtina |
Rok vydání: | 1999 |
Předmět: |
mice
Ovalbumin NOS1 Immunology Inflammation Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation nitric oxide medicine Immunology and Allergy Animals Humans Lung Methacholine Chloride 030304 developmental biology Asthma Mice Knockout 0303 health sciences biology business.industry nitric oxide synthase Histocytochemistry Articles Pneumonia respiratory system asthma medicine.disease 3. Good health respiratory tract diseases Nitric oxide synthase Isoenzymes Plethysmography Disease Models Animal 030228 respiratory system chemistry Gene Targeting biology.protein Methacholine Calcium medicine.symptom business Bronchoalveolar Lavage Fluid medicine.drug allergen |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
Popis: | Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma. |
Databáze: | OpenAIRE |
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