Research Article
Carole Planès and Nadia H. Randrianarison contributed equally to this study.
Received: 21 April 2009; Revised: 26 August 2009; Accepted: 7 September 2009
10.1002/emmm.200900050 About DOI
ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1 |
| Carole Planès 1 2 3, Nadia H. Randrianarison 2 4, Roch-Philippe Charles 1, Simona Frateschi 1, Françoise Cluzeaud 2 4, Grégoire Vuagniaux 5, Paul Soler 4 6, Christine Clerici 2 4, Bernard C. Rossier 1, Edith Hummler 1 * |
| 1Département de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland 2INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3, Paris, France 3EA 2363, Université Paris 13, Bobigny, France 4Université Denis Diderot - Paris 7, Paris, France 5Debiopharm SA, Lausanne, Switzerland 6INSERM, U700, Paris, France |
| email: Edith Hummler (edith.hummler@unil.ch) |
*Correspondence to Edith Hummler, Tel: +41 21 692 5357; Fax: +41 21 692 53 55;
Carole Planès and Nadia H. Randrianarison contributed equally to this study.Funded by:
Swiss National Foundation; Grant Number: FNRS # 3100AO-102125/1, FNRS # 3100-061966
| Keywords |
 -agonist elastase prostasin sodium channel alveolar epithelium |
| 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 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 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. |
Received: 21 April 2009; Revised: 26 August 2009; Accepted: 7 September 2009
| Digital Object Identifier (DOI) |
10.1002/emmm.200900050 About DOI
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