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Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress

  • Cell and Molecular Physiology
  • Published:
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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·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 osmolarity-dependent increase (up to ∼1.5 times) in epithelial P f which was of similar magnitude in cystic fibrosis (CF) and non-CF spheroids. The effect saturated at ∼450 mOsm·l−1 and at ∼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.

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Acknowledgements

We 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 Novo-Nordisk Foundation, the Lundbeck Foundation, Zealand Pharmaceutical and the Velux Foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, DK2100, Denmark

    Peter Steen Pedersen

  2. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, DK2200, Denmark

    Peter Steen Pedersen, Thomas Hartig Braunstein, Anders Jørgensen, Niels-Henrik Holstein-Rathlou & Ole Frederiksen

  3. Department of Otolaryngology, Head and Neck Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, DK2100, Denmark

    Per Leganger Larsen

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  1. Peter Steen Pedersen
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Correspondence to Peter Steen Pedersen.

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Pedersen, P.S., Braunstein, T.H., Jørgensen, A. et al. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress. Pflugers Arch - Eur J Physiol 453, 777–785 (2007). https://doi.org/10.1007/s00424-006-0157-3

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