Overexpression of the Na-K-ATPase α2-subunit improves lung liquid clearance during ventilation-induced lung injury

被引:20
作者
Adir, Yochai [1 ,2 ]
Welch, Lynn C. [1 ]
Dumasius, Vidas [1 ]
Factor, Phillip [3 ]
Sznajder, Jacob I. [1 ]
Ridge, Karen M. [1 ,4 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA
[2] Technion Israel Inst Technol, Fac Med, Div Pulm Med, Carmel Med Ctr,Rappaport Family Inst Res Med Sci, Haifa, Israel
[3] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[4] Jesse Brown Vet Adm Med Ctr, Lakeside Div, Chicago, IL USA
关键词
acute respiratory distress syndrome; acute lung injury; experimental models; gene therapy;
D O I
10.1152/ajplung.00076.2007
中图分类号
Q4 [生理学];
学科分类号
071003 [生理学];
摘要
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 similar to 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.
引用
收藏
页码:L1233 / L1237
页数:5
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