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The Role of Na,K‐ATPase α2 Isoform in Lung Function
Author(s) -
Loreaux Elizabeth L,
Wesselkamper Scott,
DostanicLarson Iva,
Leikauf George,
Lingrel Jerry B
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a550
Subject(s) - reabsorption , lung , knockout mouse , endocrinology , medicine , homeostasis , wild type , alveolar epithelium , chemistry , pulmonary compliance , respiratory epithelium , pathology , biology , receptor , kidney , mutant , biochemistry , gene
Gas exchange across the lung epithelium requires a proper balance of fluid within the alveolar spaces, and is compromised during lung diseases such as emphysema and acute lung injury (ALI), which disable millions of Americans. Fluid reabsorption is an integral component in maintenance of this balance, and is driven by the sodium gradient regulated by Na,K‐ATPase (NKA) in lung epithelial cells. In spite of the relative expression levels of α1 NKA over α2 NKA, evidence indicates that α2 NKA, expressed in Type I lung epithelial cells, plays a major role in fluid reabsorption. Therefore, we hypothesized that α2 NKA is critical for maintaining proper fluid balance in the lung during resting states and ALI. To investigate this, we generated the α2 NKA lung‐specific knockout mouse. The lung wet‐to‐dry weight ratio did not change in resting knockout animals, suggesting that basal fluid transport is not compromised. However, the histology of knockout lungs revealed an emphysema phenotype in which there was significant hyperinflation of the alveolar spaces. This was confirmed through an increase in compliance (WT=0.066+/−0.002, KO=0.092+/−.003 mL/cmH 2 O) and a decrease in elastance (WT=15.1+/−0.52, KO=11.0+/−0.38 cmH 2 O/mL). Paradoxically, we found that the knockout animals survived nickel‐induced ALI, while wild type littermates did not. The knockout mice displayed a decreased immune response and exacerbated airway hyperinflation. We will continue to investigate the mechanisms behind these phenotypes both at molecular and physiological levels. These data demonstrate the central importance of the α2 NKA in maintaining normal lung function.