Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration.
Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration.
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DOI：
10.1085/jgp.117.6.573
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发表时间：
2001-06
期刊：
影响因子：
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通讯作者：
Verkman AS
中科院分区：
文献类型：
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作者：
Song Y;Jayaraman S;Yang B;Matthay MA;Verkman AS
哺乳动物气道和肺中有几种水通道蛋白型的水通道表达：AQP1在微血管内皮中表达，AQP3在上气道上皮中表达，AQP4在上、下气道上皮中表达，AQP5在肺泡上皮中表达。开发了新的定量方法来比较野生型小鼠和缺乏这些水通道蛋白的敲除小鼠的气道液体运输相关功能。下气道加湿（通过气管切开术测量干燥空气机械通气时的空气含水量）在野生型小鼠中效率为54-56%，而在AQP1/AQP5或AQP3/AQP4双敲除小鼠中仅降低3-4%。通过气管切开术呼吸的小鼠上呼吸道通过干燥空气获得的湿度测量，随着通气从20 ml/min增加到220 ml/min，上呼吸道湿度从91%下降到50%，在AQP3/AQP4基因敲除小鼠中下降了3-5%。采用荧光探针和共聚焦比成像显微镜在体内测定气管内气道表面液体的深度和盐浓度。野生型小鼠气道表面液体深度为45±5 μm， [Na+]为115±4 mM， AQP3/AQP4基因敲除小鼠气道表面液体深度差异无统计学意义。通过体内滴注/取样法测量，AQP3/AQP4缺失使上呼吸道渗透性降低了约40%。在进行这些测量时，我们发现上呼吸道中有一种新的对阿米洛利敏感的等摩尔流体吸收过程（5分钟13%），不受水通道蛋白缺失的影响。这些结果建立了小鼠气道的流体运输特性，并表明水通道蛋白在气道湿化、ASL水化和等摩尔流体吸收中最多起次要作用。
Several aquaporin-type water channels are expressed in mammalian airways and lung: AQP1 in microvascular endothelia, AQP3 in upper airway epithelia, AQP4 in upper and lower airway epithelia, and AQP5 in alveolar epithelia. Novel quantitative methods were developed to compare airway fluid transport–related functions in wild-type mice and knockout mice deficient in these aquaporins. Lower airway humidification, measured from the moisture content of expired air during mechanical ventilation with dry air through a tracheotomy, was 54–56% efficient in wild-type mice, and reduced by only 3–4% in AQP1/AQP5 or AQP3/AQP4 double knockout mice. Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3–5% in AQP3/AQP4 knockout mice. The depth and salt concentration of the airway surface liquid in trachea was measured in vivo using fluorescent probes and confocal and ratio imaging microscopy. Airway surface liquid depth was 45 ± 5 μm and [Na+] was 115 ± 4 mM in wild-type mice, and not significantly different in AQP3/AQP4 knockout mice. Osmotic water permeability in upper airways, measured by an in vivo instillation/sample method, was reduced by ∼40% by AQP3/AQP4 deletion. In doing these measurements, we discovered a novel amiloride-sensitive isosmolar fluid absorption process in upper airways (13% in 5 min) that was not affected by aquaporin deletion. These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption.