Surface fluid absorption and secretion in small airways

Key points •  Using a small glass capillary, an Ussing chamber was designed and used to measure electrical properties across very small pieces (<1 mm2) of freshly dissected epithelia. •  The system was applied to small airways of the lung to show that fluids on the airway surfaces are constantly being simultaneously secreted and absorbed. •  A new model proposes that the accordion-like structure of folds and pleats in the epithelial lining of the airways serves to secrete fluid within the pleats and to absorb fluid along the folds so that fluid levels on the airway surfaces are maintained automatically and airways do not flood or become too dry. •  These results help us understand the first line of lung defence against infections from bacteria and viruses and may be used to treat or prevent lung disease. Abstract  Native small airways must remain wet enough to be pliable and support ciliary clearance, but dry enough to remain patent for gas flow. The airway epithelial lining must both absorb and secrete ions to maintain a critical level of fluid on its surface. Despite frequent involvement in lung diseases, the minuscule size has limited studies of peripheral airways. To meet this challenge, we used a capillary to construct an Ussing chamber (area <1 mm2) to measure electrolyte transport across small native airways (∼1 mm o) from pig lung. Transepithelial potentials (Vt) were recorded in open circuit conditions while applying constant current pulses across the luminal surface of dissected airways to calculate transepithelial electrical conductance (Gt) and equivalent short circuit current () in the presence and absence of selected Na+ and Cl− transport inhibitors (amiloride, GlyH-101, Niflumic acid) and agonists (Forskolin + IBMX, UTP). Considered together the responses suggest an organ composed of both secreting and absorbing epithelia that constitutively and concurrently transport fluids into and out of the airway, i.e. in opposite directions. Since the epithelial lining of small airways is arranged in long, accordion-like rows of pleats and folds that run axially down the lumen, we surmise that cells within the pleats are mainly secretory while the cells of the folds are principally absorptive. This structural arrangement could provide local fluid transport from within the pleats toward the luminal folds that may autonomously regulate the local surface fluid volume for homeostasis while permitting acute responses to maintain clearance.