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Mechanosensitive ATP release maintains proper mucus hydration of airways.

Authors
  • Button, Brian1
  • Okada, Seiko F
  • Frederick, Charles Brandon
  • Thelin, William R
  • Boucher, Richard C
  • 1 Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA. [email protected]
Type
Published Article
Journal
Science Signaling
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Jun 11, 2013
Volume
6
Issue
279
Identifiers
DOI: 10.1126/scisignal.2003755
PMID: 23757023
Source
Medline
License
Unknown

Abstract

The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal autocrine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis.

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