| Title |
Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.
|
|---|---|
| Published in |
Journal of Clinical Investigation, October 1998
|
| DOI | 10.1172/jci3214 |
| Pubmed ID | |
| Authors |
P Factor, F Saldias, K Ridge, V Dumasius, J Zabner, H A Jaffe, G Blanco, M Barnard, R Mercer, R Perrin, J I Sznajder |
| 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. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 2 | 10% |
| United States | 1 | 5% |
| Unknown | 18 | 86% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 24% |
| Researcher | 4 | 19% |
| Professor > Associate Professor | 4 | 19% |
| Professor | 2 | 10% |
| Other | 1 | 5% |
| Other | 3 | 14% |
| Unknown | 2 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 10 | 48% |
| Biochemistry, Genetics and Molecular Biology | 4 | 19% |
| Veterinary Science and Veterinary Medicine | 1 | 5% |
| Arts and Humanities | 1 | 5% |
| Immunology and Microbiology | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 3 | 14% |