title: Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress.
abstract: The physical removal of viruses and bacteria on the mucociliary escalator is an important aspect of the mammalian lung's innate defense mechanism. The volume of airway surface liquid (ASL) present in the respiratory tract is a critical determinant of both mucus hydration and the rate of mucus clearance from the lung. ASL volume is maintained by the predominantly ciliated epithelium via coordinated regulation of (a) absorption, by the epithelial Na+ channel, and (b) secretion, by the Ca2+-activated Cl- channel (CaCC) and CFTR. This review provides an update on our current understanding of how shear stress regulates ASL volume height in normal and cystic fibrosis (CF) airway epithelia through extracellular ATP- and adenosine (ADO)-mediated pathways that modulate ion transport and ASL volume homeostasis. We also discuss (a) how derangement of the ADO-CFTR pathway renders CF airways vulnerable to viral infections that deplete ASL volume and produce mucus stasis, and (b) potential shear stress-dependent therapies for CF.
authors.affiliation: Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599-7248, USA. robert_tarran@med.unc.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.forename: Brian
authors.initials: B
authors.lastname: Button
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000276:immunology / Q000502:physiology*; D003550:Cystic Fibrosis / Q000276:immunology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D020545:Respiratory Mucosa / Q000276:immunology / Q000502:physiology* / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena; D013314:Stress, Mechanical; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: D007473:Ion Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator