Journal article
Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene
The Journal of clinical investigation, Vol.102(7), pp.1421-1430
10/01/1998
DOI: 10.1172/JCI3214
PMCID: PMC508990
PMID: 9769335
Abstract
Previous studies have suggested that alveolar Na,K-ATPases play an important role in active Na+ transport and lung edema clearance. We reasoned that overexpression of Na,K-ATPase subunit genes could increase Na,K-ATPase function in lung epithelial cells and edema clearance in rat lungs. To test this hypothesis we produced replication deficient human type 5 adenoviruses containing cDNAs for the rat alpha1 and beta1 Na,K-ATPase subunits (adMRCMValpha1 and adMRCMVbeta1, respectively). As compared to controls, adMRCMVbeta1 increased beta1 subunit expression and Na,K-ATPase function by 2. 5-fold in alveolar type 2 epithelial cells and rat airway epithelial cell monolayers. No change in Na,K-ATPase function was noted after infection with adMRCMValpha1. Rat lungs infected with adMRCMVbeta1, but not adMRCMValpha1, had increased beta1 protein levels and lung liquid clearance 7 d after tracheal instillation. Alveolar epithelial permeability to Na+ and mannitol was mildly increased in animals infected with adMRCMVbeta1 and a similar Escherichia coli lacZ-expressing virus. Our data shows, for the first time, that transfer of the beta1 Na,K-ATPase subunit gene augments Na,K-ATPase function in epithelial cells and liquid clearance in rat lungs. Conceivably, overexpression of Na,K-ATPases could be used as a strategy to augment lung liquid clearance in patients with pulmonary edema.
Details
- Title: Subtitle
- Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene
- Creators
- Phillip Factor - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comFernando Saldías - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comKaren Ridge - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comVidas Dumasius - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comJoseph Zabner - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comH Ari Jaffe - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comGustavo Blanco - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comMichele Barnard - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comRobert Mercer - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comRichard Perrin - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.comJacob I Sznajder - Section of Pulmonary and Critical Care Medicine, Michael Reese Hospital, Chicago, Illinois 60616, USA. pfact@aol.com
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.102(7), pp.1421-1430
- DOI
- 10.1172/JCI3214
- PMID
- 9769335
- PMCID
- PMC508990
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/01/1998
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094523702771
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