The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation.
The mucus bundles responsible for airway cleaning are retained in cystic fibrosis and by cholinergic stimulation.
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DOI：
10.1183/13993003.00457-2018
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Hansson GC
中科院分区：
文献类型：
--
作者：
Ermund A;Meiss LN;Dolan B;Bähr A;Klymiuk N;Hansson GC
尽管胆碱能刺激相反地抑制液体吸收、增加纤毛跳动频率并增加气道表面液体输送，但抗胆碱能治疗对慢性阻塞性肺疾病（如慢性阻塞性肺病）的有益效果已得到充分证明。使用猪气管支气管外植体，我们量化了基础粘液转运以及与临床使用的抗毒蕈碱化合物异丙托溴铵（Atrovent）孵育和乙酰胆碱刺激后的情况。正如预期的那样，乙酰胆碱和卡巴胆碱增加了表面液体输送。相比之下，通常在纤毛上运输的粘膜下腺体分泌的粘液束被乙酰胆碱阻止移动，这种作用被异丙托溴铵抑制。有趣的是，在缺乏功能性 CFTR 通道的猪中，粘蛋白束几乎是不动的。与野生型猪一样，卡巴胆碱刺激后囊性纤维化（CF）表面液体转运增加。停滞的 CF 粘蛋白束被捕获在附着于表面杯状细胞的气管表面上。野生型猪的粘液束可移动铜绿假单胞菌，但 CF 猪则不会。因此，乙酰胆碱将气道表面液体运输与表面粘蛋白束的运输分开，因为表面粘蛋白束受到乙酰胆碱和 CFTR 通道的动态抑制，这解释了 CF 和 COPD 的启动并打开了新的治疗窗口。
The beneficial effect of anti-cholinergic therapy for chronic obstructive pulmonary diseases like COPD is well-documented although cholinergic stimulation paradoxically inhibits liquid absorption, increases cilia beat frequency, and increases airway surface liquid transport. Using pig tracheobronchial explants, we quantified basal mucus transport as well as after incubation with by the clinically used anti-muscarinic compound ipratropium bromide (Atrovent) and stimulation with acetylcholine. As expected the surface liquid transport was increased by acetylcholine and carbachol. In contrast, the mucus bundles secreted from the submucosal glands normally transported on the cilia were stopped from moving by acetylcholine, an effect inhibited by ipratropium bromide. Interestingly, in pigs lacking a functional CFTR channel, the mucin bundles were almost immobile. As in wild-type pigs the cystic fibrosis (CF) surface liquid transport increased after carbachol stimulation. The stagnant CF mucin bundles were trapped on the tracheal surface attached to the surface goblet cells. Pseudomonas aeruginosa bacteria were moved by the mucus bundles in wild-type, but not CF pigs. Acetylcholine thus uncouples airway surface liquid transport from transport of the surface mucin bundles as the bundles are dynamically inhibited by acetylcholine and the CFTR channel, explaining initiation of CF and COPD and opening novel therapeutic windows.
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DOI：
10.1126/science.1255825
发表时间：
2014-08-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hoegger MJ;Fischer AJ;McMenimen JD;Ostedgaard LS;Tucker AJ;Awadalla MA;Moninger TO;Michalski AS;Hoffman EA;Zabner J;Stoltz DA;Welsh MJ
通讯作者：
Welsh MJ
DOI：
10.1164/rccm.201404-0670oc
发表时间：
2014-08-15
影响因子：
24.7
作者：
Birket, Susan E.;Chu, Kengyeh K.;Rowe, Steven M.
通讯作者：
Rowe, Steven M.
影响因子：
11.1
作者：
Li, Xuan;Obeidat, Ma'en;Sin, Don D.
通讯作者：
Sin, Don D.
影响因子：
9.6
作者：
AYALA, LE;AHMED, T
通讯作者：
AHMED, T
影响因子：
--
作者：
Buels, Kalmia S;Fryer, Allison D
通讯作者：
Fryer, Allison D