Abstract

Patients with acute hypoxemic respiratory failure (AHRP) develop pulmonary edema and gas exchange impairment which results in significant morbidity and mortality. Mechanically ventilated patients with AHRF have better outcomes if alveolar epithelial integrity and rapid edema reabsorption occurs. Fluid is reabsorbed from the lungs by vectorial Na+ movement out of the alveoli, via apical Na+ channels and basolaterally located Na, K-ATPases. Previous studies have demonstrated that upregulation of the alpha-1 and beta-1 subunits of the Na+ pump increase Na, K-ATPase activity in the alveolar epithelial cells (AEC) in association with increased lung edema clearance. The PI has found that not only the alpha-1 but the alpha-2 Na, K-ATPase is expressed in AEC, especially in alveolar type I epithelial cells. Thus, the focus of this application is to determine the role of alpha-2 (as compared to alpha-1) Na, K-ATPase contributing to the lung's ability to clear edema as well as the mechanisms of regulation of the Na, K-ATPase in AEC by five interrelated specific aims. Completion of the experiments may provide novel information on the role and regulation of Na, K-ATPase and active Na+ transport in normal and injured lungs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048129-09
Application #
6638328
Study Section
Lung Biology and Pathology Study Section (LBPA)
Program Officer
Gail, Dorothy
Project Start
1996-04-01
Project End
2004-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
9
Fiscal Year
2003
Total Cost
$338,769
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  Publications

Sala, Marc A; Balderas-Martínez, Yalbi Itzel; Buendía-Roldan, Ivette et al. (2018) Inflammatory pathways are upregulated in the nasal epithelium in patients with idiopathic pulmonary fibrosis. Respir Res 19:233
Amarelle, Luciano; Lecuona, Emilia (2018) A Nonhospitable Host: Targeting Cellular Factors as an Antiviral Strategy for Respiratory Viruses. Am J Respir Cell Mol Biol 59:666-667
Nin, Nicolas; Muriel, Alfonso; Peñuelas, Oscar et al. (2017) Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome. Intensive Care Med 43:200-208
Zhou, Qiyuan; Dai, Jingbo; Chen, Tianji et al. (2017) Downregulation of PKC?/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion. Cell Signal 38:49-59
Magnani, Natalia D; Dada, Laura A; Queisser, Markus A et al. (2017) HIF and HOIL-1L-mediated PKC? degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung injury. Proc Natl Acad Sci U S A 114:E10178-E10186
Lecuona, Emilia; Sznajder, Jacob I (2017) Stretching to Understand How Proteostasis and the Unfolded Protein Response Regulate Lung Injury. Am J Respir Cell Mol Biol 57:143-144
Misharin, Alexander V; Morales-Nebreda, Luisa; Reyfman, Paul A et al. (2017) Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J Exp Med 214:2387-2404
Brazee, Patricia; Dada, Laura A; Sznajder, Jacob I (2016) Role of Linear Ubiquitination in Health and Disease. Am J Respir Cell Mol Biol 54:761-8
Peteranderl, Christin; Morales-Nebreda, Luisa; Selvakumar, Balachandar et al. (2016) Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest 126:1566-80
Bharat, Ankit; Graf, Nicole; Mullen, Andrew et al. (2016) Pleural Hypercarbia After Lung Surgery Is Associated With Persistent Alveolopleural Fistulae. Chest 149:220-7

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