scholarly journals Thick airway surface liquid volume and weak mucin expression in pendrin-deficient human airway epithelia

2015 ◽  
Vol 3 (8) ◽  
pp. e12480 ◽  
Author(s):  
Hyun Jae Lee ◽  
Jee Eun Yoo ◽  
Wan Namkung ◽  
Hyung-Ju Cho ◽  
Kyubo Kim ◽  
...  
Keyword(s):  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Human Airway ◽  
Mucin Expression ◽  
Surface Liquid ◽  
Human Airway Epithelia

scholarly journals Regulation of Murine Airway Surface Liquid Volume by CFTR and Ca2+-activated Cl− Conductances

2002 ◽  
Vol 120 (3) ◽  
pp. 407-418 ◽  
Author(s):  
Robert Tarran ◽  
Matthew E. Loewen ◽  
Anthony M. Paradiso ◽  
John C. Olsen ◽  
Micheal A. Gray ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Driving Force ◽  
Apical Membrane ◽  
Critical Role ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Molecular Identity ◽  
Surface Liquid ◽  
Cl Conductance

Two Cl− conductances have been described in the apical membrane of both human and murine proximal airway epithelia that are thought to play predominant roles in airway hydration: (1) CFTR, which is cAMP regulated and (2) the Ca2+-activated Cl− conductance (CaCC) whose molecular identity is uncertain. In addition to second messenger regulation, cross talk between these two channels may also exist and, whereas CFTR is absent or defective in cystic fibrosis (CF) airways, CaCC is preserved, and may even be up-regulated. Increased CaCC activity in CF airways is controversial. Hence, we have investigated the effects of CFTR on CaCC activity and have also assessed the relative contributions of these two conductances to airway surface liquid (ASL) height (volume) in murine tracheal epithelia. We find that CaCC is up-regulated in intact murine CF tracheal epithelia, which leads to an increase in UTP-mediated Cl−/volume secretion. This up-regulation is dependent on cell polarity and is lost in nonpolarized epithelia. We find no role for an increased electrical driving force in CaCC up-regulation but do find an increased Ca2+ signal in response to mucosal nucleotides that may contribute to the increased Cl−/volume secretion seen in intact epithelia. CFTR plays a critical role in maintaining ASL height under basal conditions and accordingly, ASL height is reduced in CF epithelia. In contrast, CaCC does not appear to significantly affect basal ASL height, but does appear to be important in regulating ASL height in response to released agonists (e.g., mucosal nucleotides). We conclude that both CaCC and the Ca2+ signal are increased in CF airway epithelia, and that they contribute to acute but not basal regulation of ASL height.

scholarly journals Soluble Mediators, Not Cilia, Determine Airway Surface Liquid Volume in Normal and Cystic Fibrosis Superficial Airway Epithelia

2006 ◽  
Vol 127 (5) ◽  
pp. 591-604 ◽  
Author(s):  
Robert Tarran ◽  
Laura Trout ◽  
Scott H. Donaldson ◽  
Richard C. Boucher
Keyword(s):  
Cystic Fibrosis ◽  
Volume Regulation ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Innate Defense ◽  
Cl Secretion ◽  
Immotile Cilia ◽  
Glandular Secretion ◽  
Surface Liquid

A key aspect of the lung's innate defense system is the ability of the superficial epithelium to regulate airway surface liquid (ASL) volume to maintain a 7-μm periciliary liquid layer (PCL), which is required for cilia to beat and produce mucus flow. The mechanisms whereby airway epithelia regulate ASL height to ≥7 μm are poorly understood. Using bumetanide as an inhibitor of Cl− secretion, and nystatin as an activator of Na+ absorption, we found that a coordinated “blending” of both Cl− secretion and Na+ absorption must occur to effect ASL volume homeostasis. We then investigated how ASL volume status is regulated by the underlying epithelia. Cilia were not critical to this process as (a) ASL volume was normal in cultures from patients with primary ciliary dyskinesia with immotile cilia, and (b) in normal cultures that had not yet undergone ciliogenesis. However, we found that maneuvers that mimic deposition of excess ASL onto the proximal airways, which occurs during mucociliary clearance and after glandular secretion, acutely stimulated Na+ absorption, suggesting that volume regulation was sensitive to changes in concentrations of soluble mediators in the ASL rather than alterations in ciliary beating. To investigate this hypothesis further, we added potential “soluble mediators” to the ASL. ASL volume regulation was sensitive to a channel-activating protein (CAP; trypsin) and a CAP inhibitor (aprotinin), which regulated Na+ absorption via changes in epithelial Na+ channel (ENaC) activity in both normal and cystic fibrosis cultures. ATP was also found to acutely regulate ASL volume by inducing secretion in normal and cystic fibrosis (CF) cultures, while its metabolite adenosine (ADO) evoked secretion in normal cultures but stimulated absorption in CF cultures. Interestingly, the amount of ASL/Cl− secretion elicited by ATP/ADO was influenced by the level of CAP-induced Na+ absorption, suggesting that there are important interactions between the soluble regulators which finely tune ASL volume.

scholarly journals Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia

2020 ◽  
Vol 1 (4) ◽  
pp. 100059 ◽  
Author(s):  
Andrés Pizzorno ◽  
Blandine Padey ◽  
Thomas Julien ◽  
Sophie Trouillet-Assant ◽  
Aurélien Traversier ◽  
...  
Keyword(s):  
Airway Epithelia ◽  
Human Airway ◽  
Human Airway Epithelia

scholarly journals Chronic β2AR stimulation limits CFTR activation in human airway epithelia

JCI Insight ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
John J. Brewington ◽  
Jessica Backstrom ◽  
Amanda Feldman ◽  
Elizabeth L. Kramer ◽  
Jessica D. Moncivaiz ◽  
...  
Keyword(s):  
Airway Epithelia ◽  
Human Airway ◽  
Human Airway Epithelia

scholarly journals Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Emer P. Reeves ◽  
Kevin Molloy ◽  
Kerstin Pohl ◽  
Noel G. McElvaney
Keyword(s):  
Cystic Fibrosis ◽  
Hypertonic Saline ◽  
Mucociliary Clearance ◽  
Inflammatory Cells ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Beneficial Effects ◽  
Therapeutic Benefits ◽  
Surface Liquid ◽  
Subsequent Failure

The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

scholarly journals Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

2018 ◽  
Vol 141 (6) ◽  
pp. 2074-2084 ◽  
Author(s):  
Manel Essaidi-Laziosi ◽  
Francisco Brito ◽  
Sacha Benaoudia ◽  
Léna Royston ◽  
Valeria Cagno ◽  
...  
Keyword(s):  
Respiratory Viruses ◽  
Airway Epithelia ◽  
Human Airway ◽  
Persistent Virus ◽  
Human Airway Epithelia

scholarly journals Motile Cilia of Human Airway Epithelia Are Chemosensory

Science ◽  
2009 ◽  
Vol 325 (5944) ◽  
pp. 1131-1134 ◽  
Author(s):  
A. S. Shah ◽  
Y. Ben-Shahar ◽  
T. O. Moninger ◽  
J. N. Kline ◽  
M. J. Welsh
Keyword(s):  
Airway Epithelia ◽  
Human Airway ◽  
Motile Cilia ◽  
Human Airway Epithelia
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