TITLE

Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases

AUTHOR(S)
Shaoyan Zhang; Fortenberry, James A.; Cohen, Noam A.; Sorscher, Eric J.; Woodworth, Bradford A.
PUB. DATE
March 2009
SOURCE
American Journal of Rhinology & Allergy;Mar2009, Vol. 23 Issue 2, p149
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Methods: Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. Results: The change in forskolin-stimulated current (delta-ISC, expressed as micro-A/cm2) in murine septal (n = 19; 16.84 ± 2.09) and human sinonasal (n = 18; 12.15 ± 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 ± 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated ISC was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 μM). No forskolin-stimulated ISC was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal ISC was largely inhibited by amiloride (12.03 ± 0.66), whereas human sinonasal cultures had a very limited response (0.70 ± 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 ± 1.28; human sinonasal, 11.12 ± 1.58; murine trachea, 4.85 ± 0.49; p < 0.0001). Conclusion: Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.
ACCESSION #
48689069

 

Related Articles

  • Calcium-dependent chloride conductance in epithelia: is there a contribution by Bestrophin? Kunzelmann, Karl; Milenkovic, Vladimir M.; Spitzner, Melanie; Soria, René Barro; Schreiber, Rainer // Pflugers Archiv European Journal of Physiology;Sep2007, Vol. 454 Issue 6, p879 

    Although known for more than 20 years, the molecular identity of epithelial Ca2+-activated Cl− channels remains obscure. Previous candidate proteins did not hold initial promises, and thus, new hope is put into the recently identified family of bestrophin proteins, as they reflect many of...

  • Suppression of CFTR premature termination codons and rescue of CFTR protein and function by the synthetic aminoglycoside NB54. Rowe, Steven; Sloane, Peter; Tang, Li; Backer, Kyle; Mazur, Marina; Buckley-Lanier, Jessica; Nudelman, Igor; Belakhov, Valery; Bebok, Zsuzsa; Schwiebert, Erik; Baasov, Timor; Bedwell, David // Journal of Molecular Medicine;Nov2011, Vol. 89 Issue 11, p1149 

    Certain aminoglycosides are capable of inducing 'translational readthrough' of premature termination codons (PTCs). However, toxicity and relative lack of efficacy deter treatment with clinically available aminoglycosides for genetic diseases caused by PTCs, including cystic fibrosis (CF). Using...

  • CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium. Liqun Zhang; Button, Brian; Gabriel, Sherif E.; Burkett, Susan; Yu Yan; Skiadopoulos, Mario H.; Yan Li Dang; Vogel, Leatrice N.; McKay, Tristan; Mengos, April; Boucher, Richard C.; Collins, Peter L.; Pickles, Raymond J. // PLoS Biology;Jul2009, Vol. 7 Issue 7, p1 

    Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated...

  • Control of epithelial Na+ conductance by the cystic fibrosis transmembrane conductance regulator. Kunzelmann, Karl; Schreiber, Rainer; Nitschke, Roland; Mall, Marcus // Pflugers Archiv European Journal of Physiology;Jun2000, Vol. 440 Issue 2, p193 

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl– channel expressed in luminal membranes of secretory and reabsorptive epithelia. CFTR plays a predominant role in both cAMP- and Ca2+-activated secretion of electrolytes. Although Ca2+-dependent Cl–...

  • Characterisation of chloride currents across the proximal colon in Cftr TgH( neoim) 1Hgu congenic mice. Bleich, E.-M.; Leonhard-Marek, S.; Beyerbach, M.; Breves, G. // Journal of Comparative Physiology B: Biochemical, Systemic & Env;Jan2007, Vol. 177 Issue 1, p61 

    It was the aim of the present study to investigate chloride secretion across the proximal colon of Cftr TgH( neoim) 1Hgu congenic mice. Stripped epithelia were incubated in Ussing chambers and the electrophysiological data were compared between cystic fibrosis (CF) animals and wild type (WT)...

  • Calcium-pump inhibitors induce functional surface expression of ΔF508-CFTR protein in cystic fibrosis epithelial cells. Egan, Marie E.; Glöckner-Pagel, Judith; Ambrose, Catherine A.; Cahill, Paula A.; Pappoe, Lamiko; Balamuth, Naomi; Cho, Edward; Canny, Susan; Wagner, Carsten A.; Geibel, John; Caplan, Michael J. // Nature Medicine;May2002, Vol. 8 Issue 5, p485 

    The most common mutation in cystic fibrosis, ΔF508, results in a cystic fibrosis transmembrane conductance regulator (CFTR) protein that is retained in the endoplasmic reticulum (ER). Retention is dependent upon chaperone proteins, many of which require Ca++ for optimal activity. Interfering...

  • Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells. Vareille, Marjolaine; Kieninger, Elisabeth; Alves, Marco P.; Kopf, Brigitte S.; Moller, Alexander; Geiser, Thomas; Johnston, Sebastian L.; Edwards, Michael R.; Regamey, Nicolas // Thorax;Jun2012, Vol. 67 Issue 6, p517 

    BackgroundRhinoviruses are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to rhinovirus-induced CF exacerbations are poorly understood. It is hypothesised that there is a deficient innate...

  • Towards an in vitro model of cystic fibrosis small airway epithelium: characterisation of the human bronchial epithelial cell line CFBE41o-. Ehrhardt, Carsten; Collnot, Eva-Maria; Baldes, Christiane; Becker, Ulrich; Laue, Michael; Kwang-Jin Kim; Lehr, Claus-Michael // Cell & Tissue Research;Feb2006, Vol. 323 Issue 3, p405 

    The CFBE41o- cell line was generated by transformation of cystic fibrosis (CF) tracheo-bronchial cells with SV40 and has been reported to be homozygous for the ΔF508 mutation. A systematic characterisation of these cells, which however, is a pre-requisite for their use as an in vitro model,...

  • Retraction. Vareille, Marjolaine; Kieninger, Elisabeth; Alves, Marco P.; Kopf, Brigitte S.; Möller, Alexander; Geiser, Thomas; Johnston, Sebastian L.; Edwards, Michael R.; Regamey, Nicolas // Thorax;Sep2013, Vol. 68 Issue 9, p886 

    A correction to the article "Impaired Type I and Type III Interferon Induction and Rhinovirus Control in Human Cystic Fibrosis Airway Epithelial Cells." that was published in the 2012 issue is presented.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics