Authors: Peter Steen Pedersen Thomas Hartig Braunstein Anders Jørgensen Per Leganger Larsen NielsHenrik HolsteinRathlou Ole Frederiksen
Publish Date: 2006/10/17
Volume: 453, Issue: 6, Pages: 777-785
Abstract
Osmotic water permeability P f was measured in spheroidshaped human nasal airway epithelial explants preexposed to increasing levels of hyperosmotic stress The fluidfilled 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·l−1 Continuous diameter measurements also allowed determination of spontaneous fluid absorption Hyperosmotic pretreatment increase from 300 up to 600 mOsm·l−1 caused a time and osmolaritydependent increase up to ∼15 times in epithelial P f which was of similar magnitude in cystic fibrosis CF and nonCF spheroids The effect saturated at ∼450 mOsm·l−1 and at ∼24 h Expression of aquaporin5 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 nonCF spheroids and were not significantly influenced by hyperosmotic stress The results suggest that hyperosmotic stress is an important activator of AQP5 in human airway epithelium leading to significantly increased transepithelial water permeabilityWe thank the staff from the ENT surgery RH Dr N Rasmussen and Dr H Nielsen for their help during this study This work was supported by grants from the Danish Research Council SSVF the NovoNordisk Foundation the Lundbeck Foundation Zealand Pharmaceutical and the Velux Foundation
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