Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Although aqua porin 5 (AQP5) is the major water channel expressed in alveol ar type I cells in the lung, its actual role in the lung is a matter of con siderable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is als o detected in alveolar type II cells, and in tracheal and bronchial epithel ium. Aqp5 knockout (Aqp5(-/-)) mice were used to analyze AQP5 function in p ulmonary physiology. Compared with Aqp5(+/+) mice, Aqp5(-/-) mice show a si gnificantly increased concentration-dependent bronchoconstriction to intrav enously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a mea sure of bronchoconstriction, was significantly enhanced in Aqp5(-/-) mice c hallenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5(-/-) mice was not due to differenc es in tracheal smooth muscle contractility in isolated preparations or to a ltered levels of surfactant protein B. These data suggest a novel pathway b y which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyper responsiveness associated with asthma bracket genetic intervals on human ch romosome 12q and mouse chromosome 15, which contain the Aqp5 gene.