Borok Zea, Verkman A S
Will Rogers Institute Pulmonary Research Center, Department of Medicine, University of Southern California, Los Angeles 90033-3721, USA.
J Appl Physiol (1985). 2002 Dec;93(6):2199-206. doi: 10.1152/japplphysiol.01171.2001.
Water transport across epithelial and endothelial barriers in bronchopulmonary tissues occurs during airway hydration, alveolar fluid transport, and submucosal gland secretion. Many of the tissues involved in these processes are highly water permeable and express aquaporin (AQP) water channels. AQP1 is expressed in microvascular endothelia throughout the lung and airways, AQP3 in epithelia in large airways, AQP4 in epithelia throughout the airways, and AQP5 in type I alveolar epithelial cells and submucosal gland acinar cells. The expression of some of these AQPs increases near the time of birth and is regulated by growth factors, inflammation, and osmotic stress. Transgenic mouse models of AQP deletion have provided information about their physiological role. In lung, AQP1 and AQP5 provide the principal route for osmotically driven water transport; however, alveolar fluid clearance in the neonatal and adult lung is not affected by AQP deletion nor is lung CO(2) transport or fluid accumulation in experimental models of lung injury. In the airways, AQP3 and AQP4 facilitate water transport; however, airway hydration, regulation of the airway surface liquid layer, and isosmolar fluid absorption are not impaired by AQP deletion. In contrast to these negative findings, AQP5 deletion in submucosal glands in upper airways reduced fluid secretion and increased protein content by greater than twofold. Thus, although AQPs play a major physiological role outside of the airways and lung, AQPs appear to be important mainly in airway submucosal gland function. The substantially slower rates of fluid transport in airways, pleura, and lung compared with renal and some secretory epithelia may account for the apparent lack of functional significance of AQPs at these sites. However, the possibility remains that AQPs may play a role in lung physiology under conditions of stress and/or injury not yet tested or in functions unrelated to transepithelial fluid transport.
支气管肺组织上皮和内皮屏障的水转运发生在气道水合、肺泡液体转运和黏膜下腺分泌过程中。参与这些过程的许多组织具有高度的水渗透性，并表达水通道蛋白（AQP）水通道。AQP1在整个肺和气道的微血管内皮中表达，AQP3在大气道的上皮中表达，AQP4在整个气道的上皮中表达，AQP5在I型肺泡上皮细胞和黏膜下腺泡细胞中表达。其中一些AQP的表达在出生时附近增加，并受生长因子、炎症和渗透压应激的调节。AQP缺失的转基因小鼠模型提供了有关其生理作用的信息。在肺中，AQP1和AQP5为渗透驱动的水转运提供主要途径；然而，新生儿和成年肺中的肺泡液体清除不受AQP缺失的影响，肺损伤实验模型中的肺二氧化碳转运或液体蓄积也不受影响。在气道中，AQP3和AQP4促进水转运；然而，气道水合、气道表面液体层的调节和等渗液体吸收不受AQP缺失的损害。与这些阴性结果相反，上呼吸道黏膜下腺中AQP5的缺失减少了液体分泌，并使蛋白质含量增加了两倍以上。因此，尽管AQP在气道和肺之外发挥主要生理作用，但AQP似乎主要在气道黏膜下腺功能中起重要作用。与肾和一些分泌上皮相比，气道、胸膜和肺中的液体转运速率明显较慢，这可能解释了这些部位AQP明显缺乏功能意义的原因。然而，AQP仍有可能在尚未测试的应激和/或损伤条件下的肺生理中发挥作用，或在与跨上皮液体转运无关的功能中发挥作用。
