Author:
Joo Nam Soo,Cho Hyung-Ju,Shinbashi Meagan,Choi Jae Young,Milla Carlos E.,Engelhardt John F.,Wine Jeffrey J.
Abstract
AbstractMucus 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.
Funder
Cystic Fibrosis Foundation
Cystic Fibrosis Research Inc.
National Institute of Health
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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