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Effects of hyperosmotic stress on cultured airway epithelial cells

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Abstract

Inhalation of hyperosmotic solutions (salt, mannitol) has been used in the treatment of patients with cystic fibrosis or asthma, but the mechanism behind the effect of hyperosmotic solutions is unclear. The relation between osmolarity and permeability changes was examined in an airway cell line by the addition of NaCl, NaBr, LiCl, mannitol, or xylitol (295–700 mOsm). Transepithelial resistance was measured as an indicator of the tightness of the cultures. Cell-cell contacts and morphology were investigated by immunofluorescence and by transmission electron microscopy, with lanthanum nitrate added to the luminal side of the epithelium to investigate tight junction permeability. The electrolyte solutions caused a significant decrease in transepithelial resistance from 450 mOsm upwards, when the hyperosmolar exposure was gradually increased from 295 to 700 mOsm; whereas the nonelectrolyte solutions caused a decrease in transepithelial resistance from 700 mOsm upwards. Old cultures reacted in a more rigid way compared to young cultures. Immuno-fluorescence pictures showed weaker staining for the proteins ZO-1, claudin-4, and plakoglobin in treated samples compared to the control. The ultrastructure revealed an increased number of open tight junctions as well as a disturbed morphology with increasing osmolarity, and electrolyte solutions opened a larger proportion of tight junctions than nonelectrolyte solutions. This study shows that hyperosmotic solutions cause the opening of tight junctions, which may increase the permeability of the paracellular pathway and result in increased transepithelial water transport.

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Acknowledgements

The expert help with discussing and reviewing the electron micrographs with Dr. Agneta Lukinius as well as the expert technical assistance of Marianne Ljungkvist and Leif Ljung are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Medical Cell Biology, University of Uppsala, P.O. Box 571, 75123, Uppsala, Sweden

    Harriet Nilsson, Anca Dragomir, Anders Ahlander, Marie Johannesson & Godfried M. Roomans

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  1. Harriet Nilsson
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  2. Anca Dragomir
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  3. Anders Ahlander
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  4. Marie Johannesson
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  5. Godfried M. Roomans
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Corresponding author

Correspondence to Harriet Nilsson.

Additional information

This study was supported by the Swedish Asthma and Allergy Association and the Swedish Heart Lung Foundation.

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Nilsson, H., Dragomir, A., Ahlander, A. et al. Effects of hyperosmotic stress on cultured airway epithelial cells. Cell Tissue Res 330, 257–269 (2007). https://doi.org/10.1007/s00441-007-0482-7

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  • DOI: https://doi.org/10.1007/s00441-007-0482-7

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