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

Nam Soo Joo; Hyung-Ju Cho; Meagan Shinbashi; Jae Young Choi; Carlos E. Milla; John F. Engelhardt; Jeffrey J. Wine

doi:10.1038/s41598-021-98122-5

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

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

Nam Soo Joo, Hyung-Ju Cho, Meagan Shinbashi, Jae Young Choi, Carlos E. Milla, John F. Engelhardt and Jeffrey J. Wine

Scientific reports, Vol.11(1), pp.18828-18828

09/22/2021

DOI: 10.1038/s41598-021-98122-5

PMCID: PMC8458446

PMID: 34552115

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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 beta 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 similar to 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.

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Title: Subtitle: Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model
Creators: Nam Soo Joo - Stanford University
Hyung-Ju Cho - Yonsei University
Meagan Shinbashi - Stanford University
Jae Young Choi - Yonsei University
Carlos E. Milla - Stanford University
John F. Engelhardt - Roy J. and Lucille A. Carver College of Medicine
Jeffrey J. Wine - Stanford University
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.18828-18828
DOI: 10.1038/s41598-021-98122-5
PMID: 34552115
PMCID: PMC8458446
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: NATURE PORTFOLIO
Number of pages: 13
Grant note: WINE17G0; JOO19G0; ENGELH08XX0 / Cystic Fibrosis Foundation; Italian Cystic Fibrosis Research Foundation R01 HL148184-01; R01 DK047967 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NH17-001 / Cystic Fibrosis Research Inc. 75N92019C00010 / NIH Ferret Resource Center Contract; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Language: English
Date published: 09/22/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984284347602771

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