Document Type
Article
Publication Date
2001
Publication Source
Proceedings of the National Academy of Sciences of the United States of America
Abstract
Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5−/−) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5+/+ mice, Aqp5−/− mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5−/− mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5−/− mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.
Inclusive pages
14114–14119
ISBN/ISSN
1091-6490
Document Version
Postprint
Copyright
Copyright © 2001, The National Academy of Sciences
Publisher
The National Academy of Sciences
Volume
98
Peer Reviewed
yes
Issue
24
Sponsoring Agency
National Institutes of Health
eCommons Citation
Krane, Carissa M.; Fortner, Christopher N.; Hand, Arthur R.; McGraw, Dennis W.; Lorenz, John N.; Wert, Susan E.; Towne, Jennifer E.; Paul, Richard J.; Whitsett, Jeffrey A.; and Menon, Anil G., "Aquaporin 5-Deficient Mouse Lungs are Hyperresponsive to Cholinergic Stimulation" (2001). Biology Faculty Publications. 132.
https://ecommons.udayton.edu/bio_fac_pub/132
Included in
Biology Commons, Biotechnology Commons, Cell Biology Commons, Genetics Commons, Microbiology Commons, Molecular Genetics Commons
Comments
The document available for download is the authors' accepted manuscript, provided in compliance with publisher policy on self-archiving. Permission documentation is on file.
This work was supported by National Institutes of Health Grant RO1 DE138283 and National Institute of Environmental Health Sciences Grant ES 06096 (A.G.M.) and the National Heart Lung and Blood Institute Program of Excellence in Molecular Biology of Heart and Lung Grants HL61781 (to A.G.M. and for support of C.M.K. as a New Investigator in this program) and HL56387, and the Cystic Fibrosis Foundation (to J.A.W. and S.E.W.).