ENaC-mediated Alveolar Fluid Clearance and Lung Fluid Balance Depend on the Channel-activating Protease 1

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2010 Jan 1

PMID 20043279

Citations 63

Authors

Carole Planes

Nadia H Randrianarison

Roch-Philippe Charles

Simona Frateschi

Francoise Cluzeaud

Gregoire Vuagniaux

Paul Soler

Christine Clerici

Bernard C Rossier

Edith Hummler

Affiliations

Soon will be listed here.

Abstract

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

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