Water Permeability Adjusts Resorption in Lung Epithelia to Increased Apical Surface Liquid Volumes

Abstract

The apical surface liquid (ASL) layer covers the airways and forms a first line of defense against pathogens. Maintenance of ASL volume by airway epithelia is essential for maintaining lung function. The proteolytic activation of epithelial Na channels is believed to be the dominating mechanism to cope with increases in ASL volumes. Alternative mechanisms, in particular increases in epithelial osmotic water permeability (P), have so far been regarded as rather less important. However, most studies mainly addressed immediate effects upon apical volume expansion (AVE) and increases in ASL. This study addresses the response of lung epithelia to long-term AVE. NCI-H441 cells and primary human tracheal epithelial cells, both cultivated in air-liquid interface conditions, were used as models for the lung epithelium. AVE was established by adding isotonic solution to the apical surface of differentiated lung epithelia, and time course of ASL volume restoration was assessed by the deuterium oxide dilution method. Concomitant ion transport was investigated in Ussing chambers. We identified a low resorptive state immediately after AVE, which coincided with proteolytic ion transport activation within 10-15 minutes after AVE. The main clearance of excess ASL occurred during a delayed (hours after AVE) high resorptive state, which did not correlate with ion transport activation. Instead, high resorptive state onset coincided with an increase in P, which depended on aquaporin up-regulation. In summary, our data demonstrate that, aside from ion transport activation, modulation of P is a major mechanism to compensate for long-term AVE in lung epithelia.

Tight junctions in pulmonary epithelia during lung inflammation

“…However, other studies found that perturbations of aquaporin activity disturb transepithelial water transport and volume homeostasis in the airways [2, 32, 35, 113, 127], suggesting that TJ-independent water transport pathways through aquaporins contribute significantly to fluid transport across the airway epithelium. A more recent study now suggests that both processes occur in a different manner, where basal water transport activity is dominated by a paracellular pathway, whereas a compensatively increased water resorption is predominantly carried by an aquaporin-dependent transcellular pathway [110]. In airway epithelial cells, cldn2 localises in intracellular stores rather than at the TJs [62] and is regulated by TNF-α [86].…”

“…Besides barrier function, decreased fluid resorption across the airway epithelium is an additional susceptibility factor for lung injury and respiratory distress syndrome and worsens the clinical outcome in patients [136]. Airway and alveolar epithelia compensates for alveolar oedema formation or elevated apical surface liquid volumes by up-regulating active ion resorption [31, 39, 49, 55, 92, 123] or via increasing transcellular water permeability [110] to facilitate fluid clearance.…”

Aquaporins in the lung

“…AQP1 is unequivocally detected in plasma membranes of endothelial cells that form the barrier of blood vessels along the airways as well as within the respiratory and alveolar regions [18, 21, 29, 44, 66, 72, 89, 102, 112]. AQP3 localizes to epithelial and basal cells of the nasal epithelium [58, 72], basal, and epithelial cells of the trachea, bronchi, and bronchioli [58, 72, 90]. Along the conducting and respiratory airways, AQP3 is incorporated into the lateral membranes of epithelial cells [90].…”

“…AQP3 localizes to epithelial and basal cells of the nasal epithelium [58, 72], basal, and epithelial cells of the trachea, bronchi, and bronchioli [58, 72, 90]. Along the conducting and respiratory airways, AQP3 is incorporated into the lateral membranes of epithelial cells [90]. Also, cuboidal alveolar epithelial type II (ATII) cells express AQP3 [58, 90].…”

“…Along the conducting and respiratory airways, AQP3 is incorporated into the lateral membranes of epithelial cells [90]. Also, cuboidal alveolar epithelial type II (ATII) cells express AQP3 [58, 90]. AQP4 was detected in basal, ciliated, and glandular cells of the nasal epithelium [18, 58, 72, 89, 118] and the trachea [72].…”