Aquaporins in the lung

Abstract

The lung is the interface between air and blood where the exchange of oxygen and carbon dioxide occurs. The surface liquid that is directly exposed to the gaseous compartment covers both conducting airways and respiratory zone and forms the air-liquid interface. The barrier that separates this lining fluid of the airways and alveoli from the extracellular compartment is the pulmonary epithelium. The volume of the lining fluid must be kept in a range that guarantees an appropriate gas exchange and other functions, such as mucociliary clearance. It is generally accepted that this is maintained by balancing resorptive and secretory fluid transport across the pulmonary epithelium. Whereas osmosis is considered as the exclusive principle of fluid transport in the airways, filtration may contribute to alveolar fluid accumulation under pathologic conditions. Aquaporins (AQP) facilitate water flux across cell membranes, and as such, they provide a transcellular route for water transport across epithelia. However, their contribution to near-isosmolar fluid conditions in the lung still remains elusive. Herein, we discuss the role of AQPs in the lung with regard to fluid homeostasis across the respiratory epithelium.

Keywords: Aquaporin; Endothelium; Epithelium; Lung; Water transport.

Fig. 1

Schematic view of aquaporins. a Aquaporins contain cytosolic N- and C-terminal domains and six transmembrane spanning segments (H1 to H6). The extracellular loops (loops A, C, and E) link H1 with H2, H3 with H4, and H5 with H6. Intracellular loops (loops B and D) connect H2 with H3 and H5 with H6. The NPA motives (see text) are located in loop B N-terminal from the helix HB and in loop E N-terminal from the HE helix. b Schematic model of arrangement of the transmembrane spanning segments, the small pore helices HB and HE, as well as the NPA boxes around the water-conducting pore (shown in light blue). The obstruction of the center pore by the NPA motives according to the hour glass model is depicted. c View from above the extracellular surface on the top of an AQP tetramer. The arrangement of the transmembrane spanning segments H1 to H3 (given in orange) and H4 to H6 (given in green) is shown. Asterisks highlight the water pore of each AQP monomer. (All models were redrawn from [31, 56, 88, 100])

Fig. 2

Barrier models for water transport in the lung. a Model for the respiratory segments. Endothelium and epithelium constitute barriers in series for water flux from the vascular compartment across the interstitium to the apical surface of the airways. Osmotic pressure-driven transendothelial/transepithelial water permeability (P_f) depends on transendothelial (P_f,endo) and on transepithelial (P_f,epi) water permeability. P_f,endo and P_f,epi contribute equally to P_f. AQP5 limits P_f,epi, and AQP1 limits P_f,endo. b Model of the conducting airways. Again, endothelium and epithelium act in series as barriers for water flux from the vascular compartment across the interstitium to the apical surface of the airways. In the airway segments, P_f,epi depends on AQP4 and is approximately a magnitude lower than P_f,endo that is limited by AQP1. Hence, P_f,epi dominates P_f. GA marks glandular acini. Water permeability of the GA epithelium depends on AQP5

Fig. 3

Comparison of osmotic coupling, standing gradient osmotic flow, and sodium recirculation models for near-isotonic water transport. Colors of extracellular compartments encode for their osmolality: red > blue. a Osmotic coupling model: Water and solutes travel via a transcellular route only. Apical osmolality (P_osm,ap) almost equals basal osmolality (P_osm,ba). The model distinguishes the apical, the basolateral, and the intracellular compartment. b Standing gradient osmotic flow model: Solutes and water travel via a transcellular route. Solutes that enter the lateral intercellular space establish an osmotic gradient. Within this gradient, osmolality drops from the apical pole of the lateral intercellular space (P_osm,lis-ap) towards its basal pole (P_osm,lis-ba). P_osm,lis-ba is almost equal to the osmolality of the basal compartment (P_osm,ba). This model distinguishes the lateral interstitial space from the apical, the basal, and the intracellular compartment. c Sodium recirculation model: Water and solutes travel via a transcellular and via a paracellular route. Solutes that enter the lateral interstitial space increase its osmolality (P_osm,lis). Osmolality of the resorbed fluid that exits the lateral intercellular space is adjusted to osmolality of the basal compartment (P_osm,ba) by Na⁺ uptake across the basal cell membrane (Na⁺ recirculation). P_osm,ap is almost equal to P_osm,ba. P_osm,lis is larger than P_osm,ap and P_osm,ba. This model distinguishes the apical, the basal, the intracellular compartment, and the lateral intercellular space