title: Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress.
abstract: Osmotic water permeability (P(f )) was measured in spheroid-shaped human nasal airway epithelial explants pre-exposed to increasing levels of hyperosmotic stress. The fluid-filled spheroids, derived from nasal polyps, were lined by a single cell layer with the ciliated apical cell membrane facing the outside. The P(f ) was determined from diameter changes of the spheroids in response to changes in bathing medium osmolarity forth and back between 300 and 225 mOsm x l(-1). Continuous diameter measurements also allowed determination of spontaneous fluid absorption. Hyperosmotic pretreatment (increase from 300 up to 600 mOsm x l(-1)) caused a time- and osmolarity-dependent increase (up to approximately 1.5 times) in epithelial P(f ) which was of similar magnitude in cystic fibrosis (CF) and non-CF spheroids. The effect saturated at approximately 450 mOsm x l(-1) and at approximately 24 h. Expression of aquaporin-5 (AQP5), studied by immunofluorescence and confocal microscopy, showed an increase in parallel with the increase in P(f ) following hyperosmotic stress. The AQP5 was localized both in cytoplasmic vesicles and in apical cell membranes. Spontaneous fluid absorption rates were equal in CF and non-CF spheroids and were not significantly influenced by hyperosmotic stress. The results suggest that hyperosmotic stress is an important activator of AQP-5 in human airway epithelium, leading to significantly increased transepithelial water permeability.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen DK2100, Denmark. psp@mfi.ku.dk
authors.forename: Peter Steen
authors.initials: PS
authors.lastname: Pedersen
authors.forename: Thomas Hartig
authors.initials: TH
authors.lastname: Braunstein
authors.forename: Anders
authors.initials: A
authors.lastname: Jørgensen
authors.forename: Per Leganger
authors.initials: PL
authors.lastname: Larsen
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.forename: Ole
authors.initials: O
authors.lastname: Frederiksen
mesh_terms: D051402:Aquaporin 5 / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D009298:Nasal Polyps / Q000473:pathology; D009997:Osmotic Pressure; D010539:Permeability; D018874:Spheroids, Cellular; D014867:Water / Q000378:metabolism*
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D006982:Hypertonic Solutions; D014867:Water