Effects of airway surface liquid height on the kinetics of extracellular nucleotides in airway epithelia

2014 ◽  
Vol 363 ◽  
pp. 427-435 ◽  
Author(s):  
Tauanne D. Amarante ◽  
Jafferson K.L. da Silva ◽  
Guilherme J.M. Garcia
Keyword(s):  
Extracellular Nucleotides ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Liquid Height ◽  
Surface Liquid ◽  
Kinetics Of

scholarly journals Lipoxin A4 Stimulates Calcium-Activated Chloride Currents and Increases Airway Surface Liquid Height in Normal and Cystic Fibrosis Airway Epithelia

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37746 ◽  
Author(s):  
Valia Verrière ◽  
Gerard Higgins ◽  
Mazen Al-Alawi ◽  
Richard W. Costello ◽  
Paul McNally ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airway Surface Liquid ◽  
Lipoxin A4 ◽  
Airway Epithelia ◽  
Chloride Currents ◽  
Liquid Height ◽  
Cystic Fibrosis Airway ◽  
Surface Liquid

scholarly journals Paracellular bicarbonate flux across human cystic fibrosis airway epithelia tempers changes in airway surface liquid pH

2020 ◽  
Vol 598 (19) ◽  
pp. 4307-4320 ◽  
Author(s):  
Ian M. Thornell ◽  
Tayyab Rehman ◽  
Alejandro A. Pezzulo ◽  
Michael J. Welsh
Keyword(s):  
Cystic Fibrosis ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Cystic Fibrosis Airway ◽  
Surface Liquid

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 Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia

2020 ◽  
Vol 318 (2) ◽  
pp. L356-L365 ◽  
Author(s):  
Catharina van Heusden ◽  
Brian Button ◽  
Wayne H. Anderson ◽  
Agathe Ceppe ◽  
Lisa C. Morton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Atp Hydrolysis ◽  
Fluid Secretion ◽  
Pathological Feature ◽  
Airway Surface Liquid ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Atp Levels ◽  
Surface Liquid

Airway surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated Cl− channel controlled in part by the adenosine A2B receptor. An alternative CFTR-independent mechanism of fluid secretion is regulated by ATP via the P2Y2 receptor (P2Y2R) that activates Ca2+-regulated Cl− channels (CaCC/TMEM16) and inhibits Na+ absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface liquid (ASL) are inadequate to maintain P2Y2R-mediated fluid secretion. Therefore, inhibiting airway epithelial ecto-ATPases to increase ASL ATP levels constitutes a strategy to restore airway surface hydration in CF. Using [γ32P]ATP as radiotracer, we assessed the effect of a series of ATPase inhibitory compounds on the stability of physiologically occurring ATP concentrations. We identified the polyoxometalate [Co4(H2O)2(PW9O34)2]10− (POM-5) as the most potent and effective ecto-ATPase inhibitor in CF airway epithelial cells. POM-5 caused long-lasting inhibition of ATP hydrolysis in airway epithelia, which was reversible upon removal of the inhibitor. Importantly, POM-5 markedly enhanced steady-state levels of released ATP, promoting increased ASL volume in CF cell surfaces. These results provide proof of concept for ecto-ATPase inhibitors as therapeutic agents to restore hydration of CF airway surfaces. As a test of this notion, cell-free sputum supernatants from CF subjects were studied and found to have abnormally elevated ATPase activity, which was markedly inhibited by POM-5.

scholarly journals Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia

2020 ◽  
Vol 21 (4) ◽  
pp. 1488 ◽  
Author(s):  
Ambra Gianotti ◽  
Valeria Capurro ◽  
Livia Delpiano ◽  
Marcin Mielczarek ◽  
María García-Valverde ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Fluid Composition ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Drug Candidates ◽  
Cystic Fibrosis Airway ◽  
Functional Models ◽  
Cftr Protein ◽  
Surface Liquid

Cystic fibrosis (CF) is a genetic disease characterized by the lack of cystic fibrosis transmembrane conductance regulator (CFTR) protein expressed in epithelial cells. The resulting defective chloride and bicarbonate secretion and imbalance of the transepithelial homeostasis lead to abnormal airway surface liquid (ASL) composition and properties. The reduced ASL volume impairs ciliary beating with the consequent accumulation of sticky mucus. This situation prevents the normal mucociliary clearance, favouring the survival and proliferation of bacteria and contributing to the genesis of CF lung disease. Here, we have explored the potential of small molecules capable of facilitating the transmembrane transport of chloride and bicarbonate in order to replace the defective transport activity elicited by CFTR in CF airway epithelia. Primary human bronchial epithelial cells obtained from CF and non-CF patients were differentiated into a mucociliated epithelia in order to assess the effects of our compounds on some key properties of ASL. The treatment of these functional models with non-toxic doses of the synthetic anionophores improved the periciliary fluid composition, reducing the fluid re-absorption, correcting the ASL pH and reducing the viscosity of the mucus, thus representing promising drug candidates for CF therapy.

scholarly journals TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin

2020 ◽  
Vol 319 (2) ◽  
pp. C331-C344 ◽  
Author(s):  
Tayyab Rehman ◽  
Ian M. Thornell ◽  
Alejandro A. Pezzulo ◽  
Andrew L. Thurman ◽  
Guillermo S. Romano Ibarra ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Defense Mechanism ◽  
Primary Cultures ◽  
Secretory Cells ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Airway Diseases ◽  
Key Factor ◽  
Surface Liquid ◽  
And Function

The pH of airway surface liquid (ASL) is a key factor that determines respiratory host defense; ASL acidification impairs and alkalinization enhances key defense mechanisms. Under healthy conditions, airway epithelia secrete base ([Formula: see text]) and acid (H+) to control ASL pH (pHASL). Neutrophil-predominant inflammation is a hallmark of several airway diseases, and TNFα and IL-17 are key drivers. However, how these cytokines perturb pHASL regulation is uncertain. In primary cultures of differentiated human airway epithelia, TNFα decreased and IL-17 did not change pHASL. However, the combination (TNFα+IL-17) markedly increased pHASL by increasing [Formula: see text] secretion. TNFα+IL-17 increased expression and function of two apical [Formula: see text] transporters, CFTR anion channels and pendrin Cl−/[Formula: see text] exchangers. Both were required for maximal alkalinization. TNFα+IL-17 induced pendrin expression primarily in secretory cells where it was coexpressed with CFTR. Interestingly, significant pendrin expression was not detected in CFTR-rich ionocytes. These results indicate that TNFα+IL-17 stimulate [Formula: see text] secretion via CFTR and pendrin to alkalinize ASL, which may represent an important defense mechanism in inflamed airways.

scholarly journals Measurements of airway surface liquid height and mucus transport by fluorescence microscopy, and of ion composition by X-ray microanalysis

2004 ◽  
Vol 3 ◽  
pp. 135-139 ◽  
Author(s):  
Godfried M. Roomans ◽  
Inna Kozlova ◽  
Harriet Nilsson ◽  
Viengphet Vanthanouvong ◽  
Brian Button ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Airway Surface Liquid ◽  
Ion Composition ◽  
X Ray ◽  
Liquid Height ◽  
Surface Liquid

scholarly journals Physiological levels of lipoxin A4 inhibit ENaC and restore airway surface liquid height in cystic fibrosis bronchial epithelium

2014 ◽  
Vol 2 (8) ◽  
pp. e12093 ◽  
Author(s):  
Mazen Al-Alawi ◽  
Paul Buchanan ◽  
Valia Verriere ◽  
Gerard Higgins ◽  
Olive McCabe ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchial Epithelium ◽  
Airway Surface Liquid ◽  
Lipoxin A4 ◽  
Liquid Height ◽  
Surface Liquid
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