Aquaporin-5 dependent fluid secretion in airway submucosal glands.

Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to play an important role in airway defense and surface liquid homeostasis and in the pathogenesis of cystic fibrosis. Immunocytochemistr y revealed strong expression of aquaporin water channel AQP5 at the luminal membrane of serous epithelial cells in submucosal glands throughout the mo use nasopharynx and upper airways and AQP4 at the contralateral basolateral membrane in some glands. Novel methods were applied to measure secretion r ates and composition of gland fluid in wild type mice and knockout mice lac king AQP4 or AQP5. In mice breathing through a tracheotomy, total gland flu id output was measured from the dilution of a volume marker present in the fluid-filled nasopharynx and upper trachea. Pilocarpine-stimulated fluid se cretion was 4.3 +/- 0.4 mul/min in wild type mice, 4.9 +/- 0.9 mul/min in A QP4 null mice, and 1.9.+/- 0.3 mul/min in AQP5 null mice (p < 0.001). Simil ar results were obtained when secreted fluid was collected in the oil-fille d nasopharyngeal cavity. Real-time video imaging of fluid droplets secreted from individual submucosal glands near the larynx in living mice showed a 57 +/- 4% reduced fluid secretion rate in AQP5 null mice. Analysis of secre ted fluid showed a 2.3 +/- 0.2-fold increase in total protein in AQP5 null mice and a smaller increase in [Cl-], suggesting intact protein and salt se cretion across a relatively water impermeable epithelial barrier. Submucosa l gland morphology and density did not differ significantly in wild type ve rsus AQP5 null mice. These results indicate that AQP5 facilitates fluid sec retion in submucosal glands and that the luminal membrane of gland epitheli al cells is the rate-limiting barrier to water movement. Modulation of glan d AQP5 expression or function might provide a novel approach to treat hyper viscous gland secretions in cystic fibrosis and excessive fluid secretions in infectious or allergic bronchitis/rhinitis.