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Am J Physiol Lung Cell Mol Physiol 294: L1233-L1237, 2008. First published April 18, 2008; doi:10.1152/ajplung.00076.2007
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Overexpression of the Na-K-ATPase {alpha}2-subunit improves lung liquid clearance during ventilation-induced lung injury

Yochai Adir,1,2 Lynn C. Welch,1 Vidas Dumasius,1 Phillip Factor,3 Jacob I. Sznajder,1 and Karen M. Ridge1,4

1Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 2Division of Pulmonary Medicine, Carmel Medical Center, Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; and 4Jesse Brown Veterans Administration Medical Center-Lakeside Division, Chicago, Illinois

Submitted 27 February 2007 ; accepted in final form 9 April 2008

Mechanical ventilation with high tidal volumes (HVT) impairs lung liquid clearance (LLC) and downregulates alveolar epithelial Na-K-ATPase. We have previously reported that the Na-K-ATPase {alpha}2-subunit contributes to LLC in normal rat lungs. Here we tested whether overexpression of Na-K-ATPase {alpha}2-subunit in the alveolar epithelium would increase clearance in a HVT model of lung injury. We infected rat lungs with a replication-incompetent adenovirus that expresses Na-K-ATPase {alpha}2-subunit gene (Ad{alpha}2) 7 days before HVT mechanical ventilation. HVT ventilation decreased LLC by ~50% in untreated, sham, and Adnull-infected rats. Overexpression of Na-K-ATPase {alpha}2-subunit prevented the decrease in clearance caused by HVT and was associated with significant increases in Na-K-ATPase {alpha}2 protein abundance and activity in peripheral lung basolateral membrane fractions. Ouabain at 10–5 M, a concentration that inhibits the {alpha}2 but not the Na-K-ATPase {alpha}1, decreased LLC in Ad{alpha}2-infected rats to the same level as sham and Adnull-infected lungs, suggesting that the increased clearance in Ad{alpha}2 lungs was due to Na-K-ATPase {alpha}2 expression and activity. In summary, we provide evidence that augmentation of the Na-K-ATPase {alpha}2-subunit, via gene transfer, may accelerate LLC in the injured lung.

acute respiratory distress syndrome; acute lung injury; experimental models; gene therapy


Address for reprint requests and other correspondence: K. M. Ridge, Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern Univ., 240 E. Huron, McGaw M300, Chicago, IL 60611 (e-mail: kridge{at}northwestern.edu)






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