Jacob I. Sznajder, MD Ernest S. Bazley Professor of Medicine Chief, Pulmonary and Critical Care Medicine Mediators and mechanisms of acute lung injury - regulation of Na,K-ATPase in the alveolar epithelium Curricula: Cell Biology Molecular Biology and Genetics E-mail:   j-sznajder@northwestern.edu

In patients with acute hypoxemic respiratory failure (AHRF) lung airspaces flood with edema from damaged pulmonary vessels and alveolar membranes, thus interfering with oxygen transfer from the airspaces into the blood which results in hypoxemia, hypercapnia and death if corrective measures are not taken. Although most patients with AHRF die from complications of multiple-organ failure, several studies have suggested that strategies to reduce pulmonary edema are associated with shorter stays in the Intensive Care Unit and better outcomes. Several studies have demonstrated the importance of active Na+ transport in the alveolar fluid reabsorption and the survival of mechanically critically ill patients with AHRF that are placed on a mechanical respirator. Active Na+ transport in normal and injured lungs are mediated by alveolar epithelial apical Na+ channels and basolateral Na,K-ATPase. 

Na,K-ATPase maintains cellular ionic and electrochemical gradients through the hydrolysis of ATP coupled to the transport of Na+ and K+ across the plasma membrane. A functional Na,K-ATPase is a heterodimer composed of an a and b subunit. At least three isoforms of the a subunit have been described, (alpha-1, alpha-2 and alpha-3), each having different sodium affinity, ouabain sensitivity, and tissue distribution. The glycosylated b subunit is thought to be responsible for integrating the isoform into the plasma membrane; to date three b isoforms have been described. 

We study the regulation and role of the Na,K-ATPase in the lung epithelium and how this contributes to the lung ability to clear edema from the lungs. For these studies we utilize multiple approaches including cell and molecular biology in cells and monolayers as well as physiological models which allow for a "well rounded" scientific training.

Publications:

Sznajder J.I., P.Factor and D.H. Ingbar. Lung edema clearance: role of Na,K-ATPase.  J. Appl. Physiol. 93:1860-1866, 2002.

Bertorello, A., Y. Komarova, R. Efendiev, C.H. Pedemonte, I.B. Leibiger, G. Borisy and J.I. Sznajder. Analysis of Na,,K-ATPase motion and incorporation into the plasma membrane in response to G protein-coupled receptor signals in living cells..  Mol. Biol. Cell. 14:1149-1157, 2003.

Ridge K.M., W. Olivera, F. Saldias, Z. Azzam, S. Horowitz, D.H. Rutschman, P. Factor and J.I. Sznajder. Alveolar type 1 cells express the alpha 2 Na,K-ATPase which contributes to lung liquid clearance.  Circ. Res. 92:453-60, 2003.

Dada, L., N. Chandel, C. Pedemonte, K.M. Ridge, A.M. Bertorello and J.I. Sznajder. Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-æ. J. Clin. Invest. 111: 1057-1064, 2003.