Regulation of Airway Surface Liquid Volume and Mucus Transport by Active Ion Transport

2004 ◽  
Vol 1 (1) ◽  
pp. 42-46 ◽  
Author(s):  
R. Tarran
Keyword(s):  
Ion Transport ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Active Ion Transport ◽  
Surface Liquid

scholarly journals The Relative Roles of Passive Surface Forces and Active Ion Transport in the Modulation of Airway Surface Liquid Volume and Composition

2001 ◽  
Vol 118 (2) ◽  
pp. 223-236 ◽  
Author(s):  
Robert Tarran ◽  
Barbara R. Grubb ◽  
John T. Gatzy ◽  
C. William Davis ◽  
Richard C. Boucher
Keyword(s):  
Ion Transport ◽  
Liquid Layer ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Mucus Clearance ◽  
Active Ion Transport ◽  
Surface Liquid ◽  
Transport Volume ◽  
Lung Defense

Two hypotheses have been proposed recently that offer different views on the role of airway surface liquid (ASL) in lung defense. The “compositional” hypothesis predicts that ASL [NaCl] is kept low (<50 mM) by passive forces to permit antimicrobial factors to act as a chemical defense. The “volume” hypothesis predicts that ASL volume (height) is regulated isotonically by active ion transport to maintain efficient mechanical mucus clearance as the primary form of lung defense. To compare these hypotheses, we searched for roles for: (1) passive forces (surface tension, ciliary tip capillarity, Donnan, and nonionic osmolytes) in the regulation of ASL composition; and (2) active ion transport in ASL volume regulation. In primary human tracheobronchial cultures, we found no evidence that a low [NaCl] ASL could be produced by passive forces, or that nonionic osmolytes contributed substantially to ASL osmolality. Instead, we found that active ion transport regulated ASL volume (height), and that feedback existed between the ASL and airway epithelia to govern the rate of ion transport and volume absorption. The mucus layer acted as a “reservoir” to buffer periciliary liquid layer height (7 μm) at a level optimal for mucus transport by donating or accepting liquid to or from the periciliary liquid layer, respectively. These data favor the active ion transport/volume model hypothesis to describe ASL physiology.

scholarly journals Functional Apical Large Conductance, Ca2+-activated, and Voltage-dependent K+ Channels Are Required for Maintenance of Airway Surface Liquid Volume

2011 ◽  
Vol 286 (22) ◽  
pp. 19830-19839 ◽  
Author(s):  
Dahis Manzanares ◽  
Carlos Gonzalez ◽  
Pedro Ivonnet ◽  
Ren-Shiang Chen ◽  
Monica Valencia-Gattas ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ion Transport ◽  
Apical Membrane ◽  
Airway Epithelial Cells ◽  
Bk Channels ◽  
Liquid Volume ◽  
Airway Surface Liquid ◽  
Airway Epithelial ◽  
Voltage Dependent ◽  
Surface Liquid

Large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels control a variety of physiological processes in nervous, muscular, and renal epithelial tissues. In bronchial airway epithelia, extracellular ATP-mediated, apical increases in intracellular Ca2+ are important signals for ion movement through the apical membrane and regulation of water secretion. Although other, mainly basolaterally expressed K+ channels are recognized as modulators of ion transport in airway epithelial cells, the role of BK in this process, especially as a regulator of airway surface liquid volume, has not been examined. Using patch clamp and Ussing chamber approaches, this study reveals that BK channels are present and functional at the apical membrane of airway epithelial cells. BK channels open in response to ATP stimulation at the apical membrane and allow K+ flux to the airway surface liquid, whereas no functional BK channels were found basolaterally. Ion transport modeling supports the notion that apically expressed BK channels are part of an apical loop current, favoring apical Cl− efflux. Importantly, apical BK channels were found to be critical for the maintenance of adequate airway surface liquid volume because continuous inhibition of BK channels or knockdown of KCNMA1, the gene coding for the BK α subunit (KCNMA1), lead to airway surface dehydration and thus periciliary fluid height collapse revealed by low ciliary beat frequency that could be fully rescued by addition of apical fluid. Thus, apical BK channels play an important, previously unrecognized role in maintaining adequate airway surface hydration.

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 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 Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion

2013 ◽  
Vol 304 (11) ◽  
pp. L746-L756 ◽  
Author(s):  
Robert Tarran ◽  
Juan R. Sabater ◽  
Tainya C. Clarke ◽  
Chong D. Tan ◽  
Catrin M. Davies ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Bacterial Resistance ◽  
Liquid Volume ◽  
Human Neutrophil Elastase ◽  
Airway Surface Liquid ◽  
Volume Depletion ◽  
Innate Defense ◽  
Mucus Clearance ◽  
Surface Liquid

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.

Sign in / Sign up

Export Citation Format

Share Document