Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Abstract

Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5 ؊/؊ ) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5 ؉/؉ mice, Aqp5 ؊/؊ mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5 ؊/؊ mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5 ؊/؊ mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.A quaporin 5 (AQP5) is a mercury-sensitive water channel expressed in mouse salivary gland acinar cells, alveolar type I cells, lacrimal glands, and the eye (1-3). However, the function of AQP5 in mouse lung physiology and pathophysiology is largely unknown. Recent studies have explored the regulation of Aqp5 gene expression in normal and disease states. In a mouse model of acute lung injury, AQP5 mRNA and protein expression were significantly decreased in association with pulmonary inflammation and edema resulting from adenoviral infection (4). Moreover, AQP5 expression in a murine lung epithelial cell line (MLE-12) is modulated by the proinf lammatory cytokine TNF-␣ through an nuclear factor (NF)-B-dependent pathway (5). Keratinocyte growth factor also has been shown to mediate the differentiation status of alveolar epithelial cells and AQP5 expression (6). However, a clear understanding of AQP5 function in the lung remains to be discerned.Previously published studies have addressed functional questions limited to the examination of the role of AQP5 in type I cells in fluid clearance and airspace-capillary osmotic water permeability. Of significance, isolated perfused lungs from Aqp5 Ϫ/Ϫ mice were shown to have a 10-fold reduction in airspace-capillary osmotic water permeability (7). Experiments addressing the role of AQP5 in alveolar fluid clearance failed to indicate a role for AQP5 in this process under certain physiological conditions (8). Based on the results of these studies, some have concluded that AQP5 does not play a major role in lung physiology. Contrary to these conclusions, the data reported here clearly define a...

Fluctuation of Aquaporin 1, 5, and 9 Expression in the Pig Oviduct during the Estrous Cycle and Early Pregnancy

“…4G2-L2) of the pig oviduct. Consistent with previous findings seen in the lung tissues of mice, rats, pigs, and humans Krane et al 2001;Skowronski 2010;Kreda et al 2001), the AQP5 antibody noticeably stained (Fig. 4U) the apical membrane of type I porcine pulmonary epithelial cells as a positive control.…”

Perlecan Domain IV Peptide Stimulates Salivary Gland Cell AssemblyIn Vitro

“…Lack of AQP5 decreased rates of salivary secretion in mice. 16,17 AQP5 expression in apical membrane of acini in salivary gland tissue revealed their secretory abilities. Because epithelial cells must be polarized to secrete fluid unidirectionally, the expression of AQP5 at sites of selfassembly in cultured cells revealed their polarization and secretory potential.…”

<em>In vitro</em> Measurements of Tracheal Constriction Using Mice

“…Some examples include analysis of gene knockouts of ion channels 17,20,25,26 , metabotropic receptors 27,28,29,30 , and downstream signaling cascades 31 . In addition, the antigen challenged mouse is frequently used for asthma studies 32 and the in vitro trachea preparation provides a useful assay for changes in contractility that ensues following development of asthma.…”