TY - JOUR
T1 - Alveolar type 1 cells express the α2 Na,K-ATPase, which contributes to lung liquid clearance
AU - Ridge, K. M.
AU - Olivera, W. G.
AU - Saldias, F.
AU - Azzam, Z.
AU - Horowitz, S.
AU - Rutschman, D. H.
AU - Dumasius, V.
AU - Factor, P.
AU - Sznajder, J. I.
PY - 2003/3/7
Y1 - 2003/3/7
N2 - 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 α1 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 α1 and α2 Na,K-ATPase isoforms. In isolated, ouabain-perfused rat lungs, the α2 Na,K-ATPase in AT1 cells mediated 60% of the basal lung liquid clearance. The β-adrenergic agonist isoproterenol increased lung liquid clearance by preferentially upregulating the α2 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 α2 gene (Adα2), which resulted in the overexpression of the α2 Na,K-ATPase protein and caused a 2-fold increase in Na,K-ATPase activity. Spontaneously breathing rats were also infected with Adα2, which increased α2 protein abundance and resulted in a ≈250% increase in lung liquid clearance. These studies provide the first evidence that α2 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 β-adrenergic receptor or by adenovirus-mediated overexpression of the α2 Na,K-ATPase.
AB - 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 α1 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 α1 and α2 Na,K-ATPase isoforms. In isolated, ouabain-perfused rat lungs, the α2 Na,K-ATPase in AT1 cells mediated 60% of the basal lung liquid clearance. The β-adrenergic agonist isoproterenol increased lung liquid clearance by preferentially upregulating the α2 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 α2 gene (Adα2), which resulted in the overexpression of the α2 Na,K-ATPase protein and caused a 2-fold increase in Na,K-ATPase activity. Spontaneously breathing rats were also infected with Adα2, which increased α2 protein abundance and resulted in a ≈250% increase in lung liquid clearance. These studies provide the first evidence that α2 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 β-adrenergic receptor or by adenovirus-mediated overexpression of the α2 Na,K-ATPase.
KW - Alveolar fluid reabsorption
KW - Alveolar type 1 cells
KW - Alveolar type 2 cells
KW - α1 and α2 Na,K-ATPase
UR - http://www.scopus.com/inward/record.url?scp=0037423820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037423820&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000059414.10360.F2
DO - 10.1161/01.RES.0000059414.10360.F2
M3 - Article
C2 - 12600893
AN - SCOPUS:0037423820
VL - 92
SP - 453
EP - 460
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 4
ER -