title: Alveolar type 1 cells express the alpha2 Na,K-ATPase, which contributes to lung liquid clearance.
abstract: The alveolar epithelium is composed of alveolar type 1 (AT1) and alveolar type 2 (AT2) cells, which represent approximately 95% and approximately 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 alpha1 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 alpha1 and alpha2 Na,K-ATPase isoforms. In isolated, ouabain-perfused rat lungs, the alpha2 Na,K-ATPase in AT1 cells mediated 60% of the basal lung liquid clearance. The beta-adrenergic agonist isoproterenol increased lung liquid clearance by preferentially upregulating the alpha2 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 alpha2 gene (Adalpha2), which resulted in the overexpression of the alpha2 Na,K-ATPase protein and caused a 2-fold increase in Na,K-ATPase activity. Spontaneously breathing rats were also infected with Adalpha2, which increased alpha2 protein abundance and resulted in a approximately 250% increase in lung liquid clearance. These studies provide the first evidence that alpha2 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 beta-adrenergic receptor or by adenovirus-mediated overexpression of the alpha2 Na,K-ATPase.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, Ill 60611, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
authors.forename: W G
authors.initials: WG
authors.lastname: Olivera
authors.forename: F
authors.initials: F
authors.lastname: Saldias
authors.forename: Z
authors.initials: Z
authors.lastname: Azzam
authors.forename: S
authors.initials: S
authors.lastname: Horowitz
authors.forename: D H
authors.initials: DH
authors.lastname: Rutschman
authors.forename: V
authors.initials: V
authors.lastname: Dumasius
authors.forename: P
authors.initials: P
authors.lastname: Factor
authors.forename: J I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D010042:Ouabain / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol