Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model

Abstract Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically in...

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Autores principales:	Nam Soo Joo, Hyung-Ju Cho, Meagan Shinbashi, Jae Young Choi, Carlos E. Milla, John F. Engelhardt, Jeffrey J. Wine
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/91154804265f4012ae9f1330a2cf12f1
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spelling	oai:doaj.org-article:91154804265f4012ae9f1330a2cf12f12021-12-02T17:26:49ZCombined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model10.1038/s41598-021-98122-52045-2322https://doaj.org/article/91154804265f4012ae9f1330a2cf12f12021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98122-5https://doaj.org/toc/2045-2322Abstract Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+ absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.Nam Soo JooHyung-Ju ChoMeagan ShinbashiJae Young ChoiCarlos E. MillaJohn F. EngelhardtJeffrey J. WineNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nam Soo Joo Hyung-Ju Cho Meagan Shinbashi Jae Young Choi Carlos E. Milla John F. Engelhardt Jeffrey J. Wine Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
description	Abstract Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+ absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.
format	article
author	Nam Soo Joo Hyung-Ju Cho Meagan Shinbashi Jae Young Choi Carlos E. Milla John F. Engelhardt Jeffrey J. Wine
author_facet	Nam Soo Joo Hyung-Ju Cho Meagan Shinbashi Jae Young Choi Carlos E. Milla John F. Engelhardt Jeffrey J. Wine
author_sort	Nam Soo Joo
title	Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
title_short	Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
title_full	Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
title_fullStr	Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
title_full_unstemmed	Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
title_sort	combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/91154804265f4012ae9f1330a2cf12f1
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Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model

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