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.

P2 Purinergic Signaling in the Distal Lung in Health and Disease

“…Efficient gas exchange and surfactant function depend on regulation of the alveolar surface liquid (ASL) volume and composition [ 152 , 153 , 154 ]. The ASL is a very thin fluid layer (an average thickness of only 0.2 µm, also termed hypophase) [ 155 ], and protects the alveolar surface from desiccation whilst providing a minimal resistance (distance) to gas exchange.…”

“…The expression and, in part, localization of several sodium, potassium and anion channels in ATI and ATII cells have been described. Yet, a definite picture of the regulation of transepithelial ion transport to maintain ASL volume under physiological, as well as pathological conditions, is still missing [ 152 , 153 , 154 , 157 , 158 , 159 ].…”

“…In general, luminal nucleotides and activation of P2Y 2 receptors induce Cl - , or HCO 3- secretion and inhibit ENaC-meditated Na + absorption [ 113 , 114 ] resulting in fluid secretion. Within the alveoli, it is generally accepted that fluid resorption prevails to maintain the relatively thin ASL and impaired Na + reabsorption is associated with the formation of pulmonary edema [ 152 , 153 ]. Hence, P2 receptor-mediated ion channel activation might not play a major role for steady-state fluid transport.…”

Lipoxin A4 ameliorates alveolar fluid clearance disturbance in lipopolysaccharide-induced lung injury via aquaporin 5 and MAPK signaling pathway

“…AQPs facilitate transcellular water flux across the epithelium of alveoli (25). Among the thirteen AQPs in mammals (25), AQP5, which especially located and expressed in the pulmonary capillary endothelial cells and type I epithelial cells, is one of the most important AQPs for water transport (10). AQP5 influenced osmotic transendothelial/transepithelial water permeability and the knockout of AQP5 even decreased the water permeability to 10-fold (26).…”

Could aquaporin modulators be employed as prospective drugs for COVID-19 related pulmonary comorbidity?

“…Earlier, the mechanism of water transport across the alveolar epithelial cells were not fully understood. On the positive side, the transendothelial/ transepithelial water flux, a two-step process involving the transport of water through the endothelium, which separates vascular and interstitial compartment followed by water transport across the epithelium came into the limelight [13] . Convincingly, the osmotically driven transcellular water flux through a mercury sensitive water channel in intact sheep lungs unveiled the aquaporin (AQP) mediated water transport in lungs [14] .…”