Transcellular water transport in lung alveolar epithelium through mercury-sensitive water channels.
The movement of water between the air space and capillary compartments is important for the maintenance of air space hydration during respiration and for reabsorption of excess alveolar fluid. We have obtained immunocytochemical and functional evidence that plasma-membrane water channels are responsible for water transport in the intact lung. Northern and quantitative immunoblot analysis showed high expression of CHIP28 (channel-forming integral membrane protein of 28 kDa) water channels in rat lung; immunocytochemistry showed CHIP28 localization to epithelial cell plasma membranes. Stopped-flow light scattering measurements of osmotic water permeability (Pf) in freshly isolated rat alveolar type II epithelial cells indicated a high Pf of 0.015 +/- 0.002 cm/s (10 degrees C) that was weakly temperature-dependent (activation energy, 4 kcal/mol) and reversibly inhibited by 78 +/- 4% by 0.5 mM HgCl2. An in situ-perfused sheep lung model was used to determine the route for water movement in intact lung. Blood-to-air-space water transport was measured by sampling air space fluid after instillation into distal air spaces of hyperosmolar saline (900 mOsm) containing radioiodinated albumin and [14C]mannitol. In seven sets of experiments, air space osmolality and radioiodinated albumin equilibrated with a t1/2 of 0.85 +/- 0.1 min. In the contralateral lung perfused with 0.5 mM HgCl2, t1/2 increased to 2.7 +/- 0.4 min; the inhibitory effect of HgCl2 was fully reversed by 5 mM 2-mercaptoethanol. These results provide direct evidence for transcellular movement of water across the alveolar epithelium in intact lung through mercury-sensitive water channels.
Folkesson
H G
HG
Department of Medicine and Physiology, University of California, San Francisco 94143-0130.
Matthay
M A
MA
Hasegawa
H
H
Kheradmand
F
F
Verkman
A S
AS
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D001834:Body Water / Q000378:metabolism*; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008628:Mercury / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep
C496022:Aqp1 protein, rat; D020346:Aquaporins; D007473:Ion Channels; D051398:Aquaporin 1; D008628:Mercury