Published ahead of print on February 8, 2007, doi:10.1165/rcmb.2006-0347OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 6, June 2007, 688-696 A more recent version of this article appeared on June 1, 2007
Submitted on September 13, 2006 Chloride-dependent Secretion of Alveolar Wall Liquid Determined by Optical-sectioning MicroscopyJens Lindert1,1 Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, SLRHC, Lung Biology Laboratory, New York, NY, United States * To whom correspondence should be addressed. 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.
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