This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 2006-0347OCv1 36/6/688    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lindert, J. Articles by Bhattacharya, J. Search for Related Content PubMed PubMed Citation Articles by Lindert, J. Articles by Bhattacharya, J.

Chloride-Dependent Secretion of Alveolar Wall Liquid Determined by Optical-Sectioning Microscopy

Lung Biology Laboratory, Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, SLRHC, New York, New York

Correspondence and requests for reprints should be addressed to Jahar Bhattacharya, 432 West 58th Street, Room 510, New York, NY 10019. E-mail: jb39{at}columbia.edu

The liquid layer lining the pulmonary alveolar wall critically determines the lung's immune defense against inhaled pathogens, because it provides a liquid milieu in the air-filled alveolus for dispersal of immune cells and defensive surfactant proteins. However, mechanisms underlying formation of the liquid are unknown. We achieved visualization of the alveolar wall liquid (AWL) in situ in mouse lungs by means of optical-sectioning microscopy. Continuous liquid secretion was present in alveoli of wild-type (WT) mice under baseline conditions. This secretion was blocked by inhibitors of the cystic fibrosis transmembrane regulator (CFTR). The secretion was absent in Cftr^–/– mice, and it was blocked when chloride was depleted from the perfusate of WT mice, providing the first evidence that CFTR-dependent chloride secretion causes AWL formation. Injected microparticles demonstrated flow of the AWL. The flow was blocked by CFTR inhibition and was absent in Cftr^–/– mice. We conclude that CFTR-dependent liquid secretion is present in alveoli of the adult mouse. Defective alveolar secretion might impair alveolar immune defense and promote alveolar disease.

Key Words: lung • mouse • CFTR • alveolar secretion • optical-sectioning microscopy

CLINICAL RELEVANCE Our studies of the liquid dynamics of the alveolar wall liquid by real-time microscopy indicate that chloride secretion causes alveolar wall liquid formation, a mechanism previously unknown. This will extend the understanding of innate immune defense.