title: Effects of hyperosmotic stress on cultured airway epithelial cells.
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.
authors.affiliation: Department of Medical Cell Biology, University of Uppsala, P.O. Box 571, 75123, Uppsala, Sweden. harriet.nilsson@mcb.uu.se
authors.forename: Harriet
authors.initials: H
authors.lastname: Nilsson
authors.forename: Anca
authors.initials: A
authors.lastname: Dragomir
authors.forename: Anders
authors.initials: A
authors.lastname: Ahlander
authors.forename: Marie
authors.initials: M
authors.lastname: Johannesson
authors.forename: Godfried M
authors.initials: GM
authors.lastname: Roomans
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D062506:Claudin-4; D051180:Desmoplakins / Q000378:metabolism / Q000648:ultrastructure; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D006982:Hypertonic Solutions / Q000493:pharmacokinetics*; D008565:Membrane Proteins / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*; D062826:Zonula Occludens-1 Protein; D051185:gamma Catenin
chemical_list: C568157:CLDN4 protein, human; D062506:Claudin-4; D051180:Desmoplakins; D006982:Hypertonic Solutions; C495292:JUP protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051185:gamma Catenin