Circulation Research. 2003
Published online before print January 30, 2003, doi: 10.1161/01.RES.0000059414.10360.F2
Published online before print January 30, 2003, doi: 10.1161/01.RES.0000059414.10360.F2
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Submitted on June 7, 2002
Revised on January 21, 2003
Accepted on January 21, 2003
Alveolar Type 1 Cells Express the 
2 Na,K-ATPase, Which Contributes to Lung Liquid Clearance
K. M. Ridge ;
From the Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, Ill; Heart and Lung Institute, Louisville, Ky; and Department of Mathematics, Northeastern Illinois University, Chicago, Ill.
* To whom correspondence should be addressed. E-mail: j-sznajder{at}northwestern.edu.
The alveolar epithelium is composed of alveolar type 1 (AT1) and alveolar type 2 (AT2) cells, which represent 
95% and 5% of the alveolar surface area, respectively. Lung liquid clearance is driven by the osmotic gradient generated by the Na,K-ATPase. AT2 cells have been shown to express the 
1 Na,K-ATPase. We postulated that AT1 cells, because of their larger surface area, should be important in the regulation of active Na+ transport. By immunofluorescence and electron microscopy, we determined that AT1 cells express both the 1 and 2 Na,K-ATPase isoforms. In isolated, ouabain-perfused rat lungs, the 2 Na,K-ATPase in AT1 cells mediated 60% of the basal lung liquid clearance. The 
-adrenergic agonist isoproterenol increased lung liquid clearance by preferentially upregulating the 2 Na,K-ATPase protein abundance in the plasma membrane and activity in alveolar epithelial cells (AECs). Rat AECs and human A549 cells were infected with an adenovirus containing the rat Na,K-ATPase 2 gene (Ad2), which resulted in the overexpression of the 2 Na,K-ATPase protein and caused a 2-fold increase in Na,K-ATPase activity. Spontaneously breathing rats were also infected with Ad2, which increased 2 protein abundance and resulted in a 250% increase in lung liquid clearance. These studies provide the first evidence that 2 Na,K-ATPase in AT1 cells contributes to most of the active Na+ transport and lung liquid clearance, which can be further increased by stimulation of the -adrenergic receptor or by adenovirus-mediated overexpression of the 2 Na,K-ATPase.
Key words: alveolar type 2 cells • alveolar type 1 cells •
1 and 2 Na,K-ATPase •
alveolar fluid reabsorption
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