Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation
Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation
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DOI：
10.1073/pnas.231273398
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发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Menon, AG
中科院分区：
文献类型：
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作者：
Krane, CM;Fortner, CN;Menon, AG
尽管水孔蛋白 5 (AQP5) 是肺 I 型肺泡细胞中表达的主要水通道，但其在肺中的实际作用仍存在很大的猜测。通过免疫组织化学染色，我们发现小鼠肺中的 AQP5 表达不仅限于 I 型细胞，还在肺泡 II 型细胞以及气管和支气管上皮中检测到。 Aqp5 敲除 (Aqp5(-/-)) 小鼠用于分析 AQP5 在肺生理学中的功能。与Aqp5(+/+)小鼠相比，Aqp5(-/-)小鼠静脉注射Ach后浓度依赖性支气管收缩显着增加，表现为总肺阻力增加和动态肺顺应性下降(P < 0.05)。同样，在接受雾化乙酰甲胆碱攻击的 Aqp5(-/-) 小鼠中，Penh（支气管收缩的测量方法）显着增强（P < 0.05）。在 Aqp5(-/-) 小鼠中观察到的对支气管收缩的过度反应并不是由于分离制剂中气管平滑肌收缩力的差异或表面活性蛋白 B 水平的改变所致。这些数据表明 AQP5 影响支气管收缩的新途径。这一观察结果特别令人感兴趣，因为研究确定了与哮喘相关的气道高反应性相关的遗传位点，包括人类 12q 染色体和小鼠 15 号染色体上的遗传区间，其中包含 Aqp5 基因。
Although aqua porin 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.