Defective fluid transport by cystic fibrosis airway epithelia.
Defective fluid transport by cystic fibrosis airway epithelia.
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囊性纤维化气道上皮的液体运输缺陷。
DOI：
10.1172/jci117087
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Welsh,MJ
中科院分区：
文献类型：
--
作者：
Smith,JJ;Karp,PH;Welsh,MJ
囊性纤维化（CF）气道上皮细胞表现出有缺陷的跨上皮电解质转运：cAMP刺激的Cl-分泌被取消，因为顶端膜囊性纤维化跨膜传导调节因子（CFTR）Cl-通道的损失，和阿米洛利敏感的Na+吸收增加两到三倍，因为阿米洛利敏感的顶端Na+渗透性增加。这些异常被认为会改变呼吸道液体，从而导致气道疾病，这是这种遗传性疾病的主要死亡原因。然而，尚未验证CF气道上皮细胞中液体转运异常的基本假设。大多数关于流体运输的推测是基于在Ussing室中短路条件下进行的Na+和Cl-运输的测量。但这些研究与体内条件不同，因为跨上皮电压和粘膜液成分保持恒定。因此，我们在不保持跨上皮电压和离子浓度梯度为零的情况下，测量了CF气道上皮原代培养物中的液体转运和粘膜电解质组成。在正常上皮细胞中，cAMP激动剂加阿米洛利刺激NaCl和液体分泌。在CF上皮细胞中，cAMP激动剂未能刺激液体或电解质分泌，这些变化与CFTR Cl-通道的丧失一致。但与基于Ussing室研究的预测形成鲜明对比的是，CF上皮吸收液体的速率并不高于正常上皮。此外，抑制Na+通道的阿米洛利未能抑制CF上皮细胞的液体吸收。这些结果对于理解CF气道疾病的发病机制以及治疗的设计和评估具有重要意义。
Cystic fibrosis (CF) airway epithelia exhibit defective transepithelial electrolyte transport: cAMP-stimulated Cl- secretion is abolished because of the loss of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, and amiloride-sensitive Na+ absorption is increased two- to threefold because of increased amiloride-sensitive apical Na+ permeability. These abnormalities are thought to alter respiratory tract fluid, thereby contributing to airway disease, the major source of mortality in this genetic disease. However, the underlying hypothesis, that fluid transport is abnormal in CF airway epithelia, has not been tested. Most conjecture about fluid transport is based on measurements of Na+ and Cl- transport performed under short circuit conditions in Ussing chambers. But such studies differ from in vivo conditions in that transepithelial voltage and mucosal fluid composition are held constant. Therefore, we measured fluid transport and mucosal electrolyte composition in primary cultures of CF airway epithelia without holding transepithelial voltage and ion concentration gradients at zero. In normal epithelia, cAMP agonists plus amiloride stimulated NaCl and fluid secretion. In CF epithelia, cAMP agonists failed to stimulate fluid or electrolyte secretion, changes consistent with the loss of CFTR Cl- channels. But in striking contrast to predictions based on Ussing chamber studies, CF epithelia absorbed fluid at a rate no greater than normal epithelia. Moreover, amiloride, which inhibits Na+ channels, failed to inhibit fluid absorption by CF epithelia. These results have important implications for understanding the pathogenesis of CF airway disease and for the design and evaluation of therapy.Images
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通过气道上皮细胞输送电解质。
影响因子：
33.6
作者：
Welsh,MJ
通讯作者：
Welsh,MJ
胰腺囊性纤维化和支气管扩张中气管支气管分泌物的成分。
影响因子：
8
作者：
W. S. Chernick;G. Barbero
通讯作者：
G. Barbero
DOI：
10.1073/pnas.88.14.6003
发表时间：
1991-07-01
影响因子：
11.1
作者：
ANDERSON, MP;WELSH, MJ
通讯作者：
WELSH, MJ
雾化阿米洛利治疗囊性纤维化肺部疾病的初步研究。
DOI：
10.1056/nejm199004263221704
发表时间：
1990
期刊：
The New England journal of medicine
影响因子：
--
作者：
Knowles,MR;Church,NL;Waltner,WE;Yankaskas,JR;Gilligan,P;King,M;Edwards,LJ;Helms,RW;Boucher,RC
通讯作者：
Boucher,RC
培养的人鼻上皮中的钠转运和细胞内钠活性。
DOI：
10.1152/ajpcell.1991.261.2.c319
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Willumsen,NJ;Boucher,RC
通讯作者：
Boucher,RC