scholarly journals Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema

2015 ◽  
Vol 3 (9) ◽  
pp. e12453 ◽  
Author(s):  
Fouad Azizi ◽  
Abdelilah Arredouani ◽  
Ramzi M. Mohammad
2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Emer P. Reeves ◽  
Kevin Molloy ◽  
Kerstin Pohl ◽  
Noel G. McElvaney

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.


2015 ◽  
Vol 3 (8) ◽  
pp. e12480 ◽  
Author(s):  
Hyun Jae Lee ◽  
Jee Eun Yoo ◽  
Wan Namkung ◽  
Hyung-Ju Cho ◽  
Kyubo Kim ◽  
...  

2013 ◽  
Vol 304 (11) ◽  
pp. L746-L756 ◽  
Author(s):  
Robert Tarran ◽  
Juan R. Sabater ◽  
Tainya C. Clarke ◽  
Chong D. Tan ◽  
Catrin M. Davies ◽  
...  

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2′-desoxy-9-( S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ∼3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC50 ∼2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.


2009 ◽  
Vol 106 (27) ◽  
pp. 11412-11417 ◽  
Author(s):  
A. Garcia-Caballero ◽  
J. E. Rasmussen ◽  
E. Gaillard ◽  
M. J. Watson ◽  
J. C. Olsen ◽  
...  

2006 ◽  
Vol 281 (38) ◽  
pp. 27942-27949 ◽  
Author(s):  
Mike M. Myerburg ◽  
Michael B. Butterworth ◽  
Erin E. McKenna ◽  
Kathryn W. Peters ◽  
Raymond A. Frizzell ◽  
...  

2011 ◽  
Vol 45 (3) ◽  
pp. 592-599 ◽  
Author(s):  
Peter R. Harvey ◽  
Robert Tarran ◽  
Stephen Garoff ◽  
Mike M. Myerburg

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