Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 88K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by De Sanctis, G. T. Articles by Drazen, J. M. Search for Related Content PubMed PubMed Citation Articles by De Sanctis, G. T. Articles by Drazen, J. M. Social Bookmarking                            What's this?

Articles

George T. De Sanctis^*, James A. MacLean, Kaoru Hamada, Sanjay Mehta^||, Jeremy A. Scott^||, Aiping Jiao^*, Chandri N. Yandava^*, Lester Kobzik, Walter W. Wolyniec^¶, Attila J. Fabian^**, Changaram S. Venugopal^*, Hartmut Grasemann^*, Paul L. Huang^**, and Jeffrey M. Drazen^*

From the ^* Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; the Department of Allergy and Clinical Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; the Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ^|| Pulmonary Division, Departments of Medicine and Pharmacology, London Health Sciences Centre, University of Western Ontario, London, Ontario N6A 4G5, Canada; ^¶ Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877; and the ^** Cardiac Unit and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

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.

Key Words: nitric oxide • allergen • mice • asthma • nitric oxide synthase

The analysis of lung resistance was performed using software provided by Andrew Jackson (Biomedical Engineering at Boston University, Boston, MA).

Abbreviations used: BAL, bronchoalveolar lavage; cNOS, constitutive NOS; eNOS, endothelial NOS; EPO, eosinophil peroxidase; iNOS, inducible NOS; KO, knockout; nNOS, neuronal NOS; NO, nitric oxide; NOS, nitric oxide synthase; R_L, pulmonary resistance; SPF, sterile pathogen-free; WT, wild-type.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS