Mucus strands from submucosal glands initiate mucociliary transport of large particles
Mucus strands from submucosal glands initiate mucociliary transport of large particles
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DOI：
10.1172/jci.insight.124863
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发表时间：
2019-01-10
期刊：
影响因子：
8
通讯作者：
Abou Alaiwa, Mahmoud H.
中科院分区：
文献类型：
--
作者：
Fischer, Anthony J.;Pino-Argumedo, Maria, I;Abou Alaiwa, Mahmoud H.
由粘膜下腺体产生的粘液是呼吸道粘膜纤毛运输（MCT）的关键组分。当粘液从粘膜下腺管排出时，粘液在气道表面形成长股。然而，这些链的功能是不确定的。为了验证粘液链促进大颗粒运输的假设，我们研究了新生猪。在体外实验中，相互连接的粘液链在气道表面上移动，附着在固定的球体上，并通过拉动它们来启动它们的运动。用乙酰甲胆碱刺激粘膜下腺体分泌增加了移动的球体的百分比，并缩短了延迟，直到粘液链开始移动球体。为了破坏粘液链，我们应用还原剂三-（2-羧乙基）膦和二硫苏糖醇。它们减少了移动球体的比例，并延迟了确实移动的球体的运动开始。我们在自主呼吸的猪中使用基于CT的微圆盘跟踪获得了类似的体内结果。乙酰甲胆碱增加了微圆盘移动的百分比，并减少了延迟，直到他们被推到气道。雾化的三-（2-羧乙基）膦可防止这些影响。一旦颗粒开始移动，还原剂在体外或体内都不会改变它们的速度。这些发现表明，粘膜下腺体产生黏液的形式股和股启动运动的大颗粒，促进他们从气道。
Mucus produced by submucosal glands is a key component of respiratory mucociliary transport (MCT). When it emerges from submucosal gland ducts, mucus forms long strands on the airway surface. However, the function of those strands is uncertain. To test the hypothesis that mucus strands facilitate transport of large particles, we studied newborn pigs. In ex vivo experiments, interconnected mucus strands moved over the airway surface, attached to immobile spheres, and initiated their movement by pulling them. Stimulating submucosal gland secretion with methacholine increased the percentage of spheres that moved and shortened the delay until mucus strands began moving spheres. To disrupt mucus strands, we applied reducing agents tris-(2-carboxyethyl)phosphine and dithiothreitol. They decreased the fraction of moving spheres and delayed initiation of movement for spheres that did move. We obtained similar in vivo results with CT-based tracking of microdisks in spontaneously breathing pigs. Methacholine increased the percentage of microdisks moving and reduced the delay until they were propelled up airways. Aerosolized tris-(2-carboxyethyl) phosphine prevented those effects. Once particles started moving, reducing agents did not alter their speed either ex vivo or in vivo. These findings indicate that submucosal glands produce mucus in the form of strands and that the strands initiate movement of large particles, facilitating their removal from airways.