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Published ahead of print on April 27, 2006, doi:10.1164/rccm.200506-987OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 3, August 2006, 299-305

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Submitted on June 27, 2005
Accepted on April 27, 2006

Ion and Fluid Transport Properties of Small Airways in Cystic Fibrosis

Sabine Blouquit1, Agathe Regnier2, Luc Dannhoffer3, Christophe Fermanian4, Emmanuel Naline3, Richard Boucher5, and Thierry Chinet3*

1 UPRES EA 220, UFR Paris Ile de France Ouest, Universite de Versailles Saint Quentin en Yvelines, Boulogne, France; Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Department of Pathology, UFR Paris Ile de France Ouest, Boulogne, France, 3 UPRES EA 220, UFR Paris Ile de France Ouest, Universite de Versailles Saint Quentin en Yvelines, Boulogne, France, 4 Clinical Research Unit, UFR Paris Ile de France Ouest, Boulogne, France, 5 Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

* To whom correspondence should be addressed. E-mail: thierry.chinet{at}apr.aphp.fr.

Rationale: Small airways constitute a major site of pathology in cystic fibrosis (CF) and provide most of the surface area of the conducting airways of the lung. However, little is known about the impact of CF on ion and fluid transport in small (bronchiolar) airways. Objectives: To describe the ion and fluid transport properties of CF bronchiolar epithelium. Methods: Primary cultures of human bronchial and bronchiolar (non-CF and CF) epithelial cells were obtained. The bioelectric properties were studied in Ussing chambers and the airway surface liquid (ASL) height was measured with confocal microscopy. Main Results: Primary cultures of {Delta}F508 CF bronchiolar epithelial cells displayed higher transepithelial resistance than non-CF cultures, whereas baseline short circuit current and amiloride-inhibitable short circuit current were similar in both preparations. The ASL height was significantly smaller in CF compared to non-CF preparations. In the presence of amiloride, addition of forskolin increased short circuit current in non-CF but not in CF bronchiolar cultures, and the ATP-induced increase in short circuit current was lower in CF than in non-CF cultures. Non-CF bronchiolar preparations displayed larger short circuit current and fluid secretion in responses to forskolin than non-CF bronchial preparations, suggesting that CFTR-dependent Cl- transport may play a more important role in the regulation of fluid transport in small airways than in large airways. Conclusion: In CF small airways, defective Cl- secretion combined with unregulated (persistent) Na+ absorption results in ASL depletion.
Key words: ion transport, bronchiole, airway surface liquid, Cystic Fibrosis Transmembrane conductance Regulator, human




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