Novel role for CFTR in fluid absorption from the distal airspaces of the lung
X Fang, N Fukuda, P Barbry, C Sartori… - The Journal of general …, 2002 - rupress.org
X Fang, N Fukuda, P Barbry, C Sartori, AS Verkman, MA Matthay
The Journal of general physiology, 2002•rupress.orgThe active absorption of fluid from the airspaces of the lung is important for the resolution of
clinical pulmonary edema. Although ENaC channels provide a major route for Na+
absorption, the route of Cl− transport has been unclear. We applied a series of
complementary approaches to define the role of Cl− transport in fluid clearance in the distal
airspaces of the intact mouse lung, using wild-type and cystic fibrosis ΔF508 mice. Initial
studies in wild-type mice showed marked inhibition of fluid clearance by Cl− channel …
clinical pulmonary edema. Although ENaC channels provide a major route for Na+
absorption, the route of Cl− transport has been unclear. We applied a series of
complementary approaches to define the role of Cl− transport in fluid clearance in the distal
airspaces of the intact mouse lung, using wild-type and cystic fibrosis ΔF508 mice. Initial
studies in wild-type mice showed marked inhibition of fluid clearance by Cl− channel …
The active absorption of fluid from the airspaces of the lung is important for the resolution of clinical pulmonary edema. Although ENaC channels provide a major route for Na+ absorption, the route of Cl− transport has been unclear. We applied a series of complementary approaches to define the role of Cl− transport in fluid clearance in the distal airspaces of the intact mouse lung, using wild-type and cystic fibrosis ΔF508 mice. Initial studies in wild-type mice showed marked inhibition of fluid clearance by Cl− channel inhibitors and Cl− ion substitution, providing evidence for a transcellular route for Cl− transport. In response to cAMP stimulation by isoproterenol, clearance was inhibited by the CFTR inhibitor glibenclamide in both wild-type mice and the normal human lung. Although isoproterenol markedly increased fluid absorption in wild-type mice, there was no effect in ΔF508 mice. Radioisotopic clearance studies done at 23°C (to block active fluid absorption) showed ∼20% clearance of 22Na in 30 min both without and with isoproterenol. However, the clearance of 36Cl was increased by 47% by isoproterenol in wild-type mice but was not changed in ΔF508 mice, providing independent evidence for involvement of CFTR in cAMP-stimulated Cl− transport. Further, CFTR played a major role in fluid clearance in a mouse model of acute volume-overload pulmonary edema. After infusion of saline (40% body weight), the lung wet-to-dry weight ratio increased by 28% in wild-type versus 64% in ΔF508 mice. These results provide direct evidence for a functionally important role for CFTR in the distal airspaces of the lung.
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