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Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

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.
AuthorsP Factor, F Saldias, K Ridge, V Dumasius, J Zabner, H A Jaffe, G Blanco, M Barnard, R Mercer, R Perrin, J I Sznajder
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 102 Issue 7 Pg. 1421-30 (Oct 01 1998) ISSN: 0021-9738 [Print] United States
PMID9769335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Macromolecular Substances
  • Pulmonary Surfactants
  • Recombinant Proteins
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
Topics
  • Adenoviruses, Human
  • Animals
  • Cell Membrane Permeability
  • Cells, Cultured
  • Epithelial Cells (cytology, physiology)
  • Genetic Vectors
  • Humans
  • Lung (cytology, physiology)
  • Macromolecular Substances
  • Male
  • Pulmonary Alveoli (cytology, enzymology, physiology)
  • Pulmonary Edema (therapy)
  • Pulmonary Surfactants (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins (biosynthesis)
  • Sodium (metabolism)
  • Sodium-Potassium-Exchanging ATPase (biosynthesis, genetics)

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