title: Mechanosensitive ATP release maintains proper mucus hydration of airways.
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.
authors.affiliation: Cystic Fibrosis Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA. bbutton@med.unc.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Button
authors.forename: Seiko F
authors.initials: SF
authors.lastname: Okada
authors.forename: Charles Brandon
authors.initials: CB
authors.lastname: Frederick
authors.forename: William R
authors.initials: WR
authors.lastname: Thelin
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology; D004548:Elasticity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009079:Mucociliary Clearance / Q000187:drug effects; D009093:Mucus / Q000166:cytology / Q000378:metabolism*; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology; D014783:Viscosity; D014867:Water / Q000378:metabolism
chemical_list: D003845:Deoxycytosine Nucleotides; D058912:Purinergic P2Y Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D014867:Water; C465279:denufosol tetrasodium; D000255:Adenosine Triphosphate; D000241:Adenosine; D014529:Uridine