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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 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.
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Details
1 Stanford University, The Cystic Fibrosis Research Laboratory, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
2 Yonsei University, Department of Otorhinolaryngology, Seoul, Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
3 Stanford University, Department of Pediatrics, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
4 University of Iowa, Department of Anatomy and Cell Biology, Carver College of Medicine, Iowa City, USA (GRID:grid.214572.7) (ISNI:0000 0004 1936 8294)