Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.
Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.
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DOI：
10.1126/science.1255825
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Welsh MJ
中科院分区：
文献类型：
--
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
囊性纤维化（CF）患者的肺部疾病是由宿主防御缺陷引起的，这种缺陷使气道易于细菌感染。患有晚期CF的人表现出粘膜纤毛转运（MCT）的缺陷，这是一个将细菌捕获并排出肺部的过程，但这是首先发生还是继发于气道重塑尚不清楚。为了评估MCT，我们跟踪了新生CF仔猪气道中不透射线微盘的运动。胆碱能刺激，刺激粘液分泌，导致微盘卡住。MCT受损不是由于睫状体周围液体消耗所致;而是CF粘膜下腺体分泌粘液链，这些粘液链仍束缚在腺管上并阻碍MCT。抑制非CF气道中的阴离子分泌复制CF异常。这些发现将受损的MCT确定为原发性缺陷，将粘膜下腺体中的CFTR损失与粘液从腺体脱离失败联系起来，并表明粘膜下腺体和栓系粘液可能是早期CF治疗的目标。
Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. People with advanced CF exhibit deficits in mucociliary transport (MCT), a process that traps and propels bacteria out of lungs, but whether this occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn CF piglets. Cholinergic stimulation, which elicits mucus secretion, caused microdisks to become stuck. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts and hindered MCT. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. These findings identify impaired MCT as a primary defect, link CFTR loss in submucosal glands to failure of mucus detachment from glands, and suggest that submucosal glands and tethered mucus may be targets for early CF treatment.
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DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
17.1
作者：
Stoltz DA;Meyerholz DK;Pezzulo AA;Ramachandran S;Rogan MP;Davis GJ;Hanfland RA;Wohlford-Lenane C;Dohrn CL;Bartlett JA;Nelson GA 4th;Chang EH;Taft PJ;Ludwig PS;Estin M;Hornick EE;Launspach JL;Samuel M;Rokhlina T;Karp PH;Ostedgaard LS;Uc A;Starner TD;Horswill AR;Brogden KA;Prather RS;Richter SS;Shilyansky J;McCray PB Jr;Zabner J;Welsh MJ
通讯作者：
Welsh MJ
影响因子：
11.1
作者：
Boucher, R. C.
通讯作者：
Boucher, R. C.
影响因子：
3.8
作者：
Lee, Robert J.;Harlow, Janice M.;Foskett, J. Kevin
通讯作者：
Foskett, J. Kevin
DOI：
10.1152/ajplung.1998.274.3.l388
发表时间：
1998-03-01
影响因子：
4.9
作者：
Wu, DXY;Lee, CYC;Widdicombe, JH
通讯作者：
Widdicombe, JH