Lung fluid transport in aquaporin-5 knockout mice.
The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia, AQP4 in airway epithelia, and AQP5 at the apical plasma membrane in type I cells of alveolar epithelia. We previously studied the role of AQP1 and AQP4 in lung fluid transport using knockout mice. Here, we examined the role of AQP5 using AQP5 knockout mice, which were recently shown to manifest defective saliva secretion. AQP5 deletion did not affect lung morphology at the light microscopic level, nor did it affect the distribution or expression of aquaporins 1, 3, or 4. Airspace-capillary osmotic water permeability (P(f)) was measured in isolated perfused lungs by pleural surface fluorescence and gravimetric methods. P(f) was reduced 10-fold by AQP5 deletion and was further reduced by 2- to 3-fold in AQP1/AQP5 double-knockout mice. Hydrostatic lung edema in response to acute increases in pulmonary artery pressure was not affected by AQP5 deletion. Active alveolar fluid absorption was measured in an in situ lung model from the increase in concentration of a volume marker in an isosmolar alveolar instillate. Interestingly, fluid absorption did not differ in litter-matched AQP5 knockout mice, nor was there an effect of AQP5 deletion when fluid absorption was maximally stimulated by pretreatment of mice with keratinocyte growth factor. These results indicate that AQP5 is responsible for the majority of water transport across the apical membrane of type I alveolar epithelial cells. The unimpaired alveolar fluid clearance in AQP5-null mice indicates that high alveolar water permeability is not required for active, near-isosmolar fluid transport.
Ma
T
T
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Fukuda
N
N
Song
Y
Y
Matthay
M A
MA
Verkman
A S
AS
D000818:Animals; D051402:Aquaporin 5; D020346:Aquaporins / Q000502:physiology*; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D011650:Pulmonary Alveoli / Q000378:metabolism
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D020346:Aquaporins; D008565:Membrane Proteins