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Mucus strands from submucosal glands initiate mucociliary transport of large particles
Anthony J. Fischer, … , Michael J. Welsh, Mahmoud H. Abou Alaiwa
Anthony J. Fischer, … , Michael J. Welsh, Mahmoud H. Abou Alaiwa
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e124863. https://doi.org/10.1172/jci.insight.124863.
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Research Article Pulmonology

Mucus strands from submucosal glands initiate mucociliary transport of large particles

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Abstract

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.

Authors

Anthony J. Fischer, Maria I. Pino-Argumedo, Brieanna M. Hilkin, Cullen R. Shanrock, Nicholas D. Gansemer, Anna L. Chaly, Keyan Zarei, Patrick D. Allen, Lynda S. Ostedgaard, Eric A. Hoffman, David A. Stoltz, Michael J. Welsh, Mahmoud H. Abou Alaiwa

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Figure 1

Mucus emerges from submucosal gland ducts as strands and forms networks.

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Mucus emerges from submucosal gland ducts as strands and forms networks....
Confocal microscopic images of mucus strands labeled with 40-nm fluorospheres (red). Reflected light from airway surface is in gray; reflected light is the white dot in center of each image. Yellow arrows indicate the direction of MCT. Submucosal gland ducts are indicated with labels. In some experiments, submucosal gland mucus secretion was stimulated with methacholine (MCH, 100 μM). (A) A mucus strands emerges and is released from a submucosal gland duct. Scale bar: 100 µm. (B) Mucus strands break free from submucosal glands and move across the surface. The asterisk indicates the free end of a moving strand. The cross indicates a strand that was attached, breaks, and then abruptly snaps back. Scale bar: 50 µm. (C) Connection forming between adjacent moving strands and subsequent release of a strand from a duct. Scale bar: 50 µm. (D) Networks of mucus strands travel over the epithelial surface under basal and methacholine-treated conditions. The dotted line is reference to selected strands at time = 0 seconds. Scale bar: 50 µm.

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ISSN 2379-3708

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