Aquaporin water channels and lung physiology

Fluid transport across epithelial and endothelial barriers occurs in the ne onatal and adult lungs. Biophysical measurements in the intact lung and cel l isolates have indicated that osmotic water permeability is exceptionally high across alveolar epithelia and endothelia and moderately high across ai rway epithelia. This review is focused on the role of membrane water-transp orting proteins, the aquaporins (AQPs), in high lung water permeability and lung physiology. The lung expresses several AQPs: AQP1 in microvascular en dothelia, AQP3 in large airways, AQP4 in large- and small-airway epithelia, and AQP5 in type I alveolar epithelial cells. Lung phenotype analysis of t ransgenic mice lacking each of these AQPs has been informative. Osmotically driven water permeability between the air space and capillary compartments is reduced similar to 10-fold by deletion of AQP1 or AQPB and reduced even more by deletion of AQP1 and AQP4 or AQP1 and AQP5 together. AQP1 deletion greatly reduces osmotically driven water transport across alveolar capilla ries but has only a minor effect on hydrostatic lung filtration, which prim arily involves paracellular water movement. However, despite the major role of AQPs in lung osmotic water permeabilities, AQP deletion has little or n o effect on physiologically important lung functions, such as alveolar flui d clearance in adult and neonatal lung, and edema accumulation after lung i njury. Although AQPs play a major role in renal and central nervous system physiology, the data to date on AQP knockout mice do not support an importa nt role of high lung water permeabilities or AQPs in lung physiology. Howev er, there remain unresolved questions about possible non-water-transporting roles of AQPs and about the role of AQPs in airway physiology, pleural flu id dynamics, and edema after lung infection.