TY - JOUR

T1 - Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress.

AU - Pedersen, Peter Steen

AU - Braunstein, Thomas Hartig

AU - Jørgensen, Anders

AU - Larsen, Per Leganger

AU - Frederiksen, Ole

AU - Holstein-Rathlou, N.-H.

N1 - Keywords: Aquaporin 5; Cystic Fibrosis; Cytoplasmic Vesicles; Female; Fluorescent Antibody Technique; Humans; Hypertonic Solutions; Male; Nasal Mucosa; Nasal Polyps; Osmotic Pressure; Permeability; Spheroids, Cellular; Water

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1007/s00424-006-0157-3

DO - 10.1007/s00424-006-0157-3

M3 - Journal article

C2 - 17043812

VL - 453

SP - 777

EP - 785

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

SN - 0031-6768

IS - 6

ER -