Mechanosensitive ATP release maintains proper mucus hydration of airways.
Mechanosensitive ATP release maintains proper mucus hydration of airways.
复制标题
DOI：
10.1126/scisignal.2003755
复制
发表时间：
2013-06-11
影响因子：
7.3
通讯作者：
Boucher RC
中科院分区：
文献类型：
--
作者：
Button B;Okada SF;Frederick CB;Thelin WR;Boucher RC
从气道清除粘液保护肺部免受吸入的有毒和感染性物质的影响。粘液层的适当水合作用能够通过呼吸道上皮细胞上纤毛的跳动来实现有效的粘液清除，并且在患有慢性阻塞性肺病和囊性纤维化的患者中，过度浓缩的粘液的清除减少。粘液运输过程中的关键步骤是气道上皮细胞感知和响应粘液水合作用的变化。我们报道了细胞外三磷酸腺苷（ATP）和腺苷是重要的管腔自分泌和旁分泌信号，调节水化的人气道上皮细胞培养物的表面通过其对顶膜嘌呤受体的作用。人气道上皮细胞培养物中的粘液水合作用通过纤毛和上覆粘液层之间的相互作用来感知：机械应变的变化，与粘液水合作用成比例，调节ATP释放速率，调节液体分泌以优化粘液层水合作用。该系统提供了一种反馈机制，通过该机制，气道将粘液水合作用保持在纤毛推进的最佳范围内。了解气道上皮细胞如何感知和响应粘液性质的变化，有助于我们了解粘液清除系统如何保护健康的气道，以及它如何在囊性纤维化等肺部疾病中失败。
The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal auto-crine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis.
登录
查看更多内容
DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
DOI：
10.1152/ajplung.90388.2008
发表时间：
2009-01
影响因子：
4.9
作者：
Kesimer, Mehmet;Kirkham, Sara;Pickles, Raymond J.;Henderson, Ashley G.;Alexis, Neil E.;DeMaria, Genevieve;Knight, David;Thornton, David J.;Sheehan, John K.
通讯作者：
Sheehan, John K.
影响因子：
4.3
作者：
Groneberg, DA;Eynott, PR;Chung, KF
通讯作者：
Chung, KF
影响因子：
15.9
作者：
CHENG, PW;BOAT, TF;BOUCHER, RC
通讯作者：
BOUCHER, RC
影响因子：
5.5
作者：
Guyot, A;Hanrahan, JW
通讯作者：
Hanrahan, JW