Chloride-Dependent Secretion of Alveolar Wall Liquid Determined by Optical-Sectioning Microscopy
- 1 June 2007
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 36 (6), 688-696
- https://doi.org/10.1165/rcmb.2006-0347oc
Abstract
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.Keywords
This publication has 47 references indexed in Scilit:
- Fluid transport across cultured rat alveolar epithelial cells: a novel in vitro systemAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- Upregulation of Alveolar Epithelial Active Na + Transport Is Dependent on β 2 -Adrenergic Receptor SignalingCirculation Research, 2004
- Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretionJCI Insight, 2002
- A novel role for cyclic nucleotide‐gated cation channels in lung liquid homeostasis in sheepThe Journal of Physiology, 1999
- LUNG SURFACTANT: A Personal PerspectiveAnnual Review of Physiology, 1997
- Barrier effects of hyperosmolar signaling in microvascular endothelium of rat lung.JCI Insight, 1997
- Demonstration That CFTR Is a Chloride Channel by Alteration of Its Anion SelectivityScience, 1991
- Intracellular chloride activities in canine tracheal epithelium. Direct evidence for sodium-coupled intracellular chloride accumulation in a chloride-secreting epithelium.JCI Insight, 1983
- Morphometric estimation of pulmonary diffusion capacity: III. The effect of increased oxygen consumption in Japanese Waltzing miceRespiration Physiology, 1971
- Improvements in demonstration of lining layer of lung alveoli by electron microscopyRespiration Physiology, 1969