Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice
Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice
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DOI：
10.1172/jci4138
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发表时间：
1999-02-01
影响因子：
15.9
通讯作者：
Verkman, AS
中科院分区：
文献类型：
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作者：
Bai, CX;Fukuda, N;Verkman, AS
哺乳动物肺表达微血管内皮细胞中的水通道水通道蛋白-1（AQP 1）和气道上皮细胞中的水通道蛋白-4（AQP 4）为了测试这些水通道是否促进空气空间、间质和毛细血管室之间的流体运动，我们测量了AQP 1和AQP 4敲除小鼠中的被动和主动流体运输。用胸膜表面荧光法测定离体灌流肺的气腔毛细血管渗透水通透性（PF）。AQP 1（-/-）小鼠的P-f显著降低（测量单位：cm/s x 0.001，SE，n = 5-10：17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP 1 [+/-]; 1.7 +/- 0.3 AQP 1 [-/-]; 12 +/- 1 AQP 4 [-/-]）。通过相关胸膜表面荧光方法测量的微血管内皮水渗透性在AQP 1（-/-）与（+/+）小鼠中降低了10倍以上，其中空气空间充满惰性全氟化碳。通过重量法和直接测量血管外肺水来测量流体静力学诱导的肺间质和肺泡水肿。两种方法都表明，AQP 1（-/-）与（+/+）小鼠相比，肺动脉压增加5-至10-cm H2O 5分钟后，肺水蓄积减少了两倍以上。使用I-125-白蛋白作为气腔液体体积标记物，在原位灌注肺中测量主动、近等渗肺泡液体吸收a）。（+/+）小鼠的J（v）（以30分钟时的液体摄取百分比测量，n = 5）为6.0 +/- 0.6（37 ℃），β-受体激动剂可将其增加至16 +/- I，阿米洛利、哇巴因或冷却至23 ℃可将其抑制至小于2.0。J（v）（含异丙肾上腺素）不受水通道蛋白缺失的影响（18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP 1 [-/-]; 16.3 +/- 1.7 AQP 4 [-/-]）。这些结果表明，在成人肺中的微血管中的渗透驱动的水运输发生通过AQP 1水通道的跨细胞途径和微血管内皮细胞是一个重要的障碍，为空气空间毛细血管渗透水运输。AQP 1促进流体静力学驱动的肺水肿，但不是肺泡液主动近等渗吸收所必需的。
The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia and aquaporin-4 (AQP4) in airway epithelia To test whether these water channels facilitate fluid movement between airspace, interstitial, and capillary compartments, we measured passive and active fluid transport in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeability (PF) was measured in isolated perfused lungs by a pleural surface fluorescence method. P-f was remarkably reduced in AQP1 (-/-) mice (measured in cm/s x 0.001, SE, n = 5-10: 17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP1 [+/-]; 1.7 +/- 0.3 AQP1 [-/-]; 12 +/- 1 AQP4 [-/-]). Microvascular endothelial water permeability, measured by a related pleural surface fluorescence method in which the airspace was filled with inert perfluorocarbon, was reduced more than 10-fold in AQP1 (-/-) vs. (+/+) mice. Hydrostatically induced lung interstitial and alveolar edema was measured by a gravimetric method and by direct measurement of extravascular lung water. Both approaches indicated a more than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to IO-cm H2O increase in pulmonary artery pressure for five minutes. Active, near-isosmolar alveolar fluid absorption a,) was measured in in situ perfused lungs using I-125-albumin as an airspace fluid volume marker. J(v) (measured in percent fluid uptake at 30 min,n = 5) in (+/+) mice was 6.0 +/- 0.6 (37 degrees C), increased to 16 +/- I by beta-agonists, and inhibited to less than 2.0 by amiloride, ouabain, or cooling to 23 degrees C. J(v) (with isoproterenol) was not affected by aquaporin deletion (18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP1 [-/-]; 16.3 +/- 1.7 AQP4 [-/-]). These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport. AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid.