Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia
| Autor: | David A. Stoltz, Michael V. Rector, Kathryn Chaloner, Philip H. Karp, Leah R. Reznikov, Jeng-Haur Chen, Alejandro A. Pezzulo, Sarah E. Ernst, Janice L. Launspach, Thomas O. Moninger, Michael J. Welsh, Joseph Zabner |
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| Rok vydání: | 2010 |
| Předmět: |
Anions
medicine.medical_specialty Cystic Fibrosis Respiratory System Sus scrofa HUMDISEASE Cystic Fibrosis Transmembrane Conductance Regulator Absorption (skin) Biology Cystic fibrosis General Biochemistry Genetics and Molecular Biology Epithelium Article Internal medicine medicine Animals Humans Respiratory system Transcellular Ion transporter Ion Transport Biochemistry Genetics and Molecular Biology(all) respiratory system medicine.disease Molecular biology Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Endocrinology medicine.anatomical_structure Animals Newborn Permeability (electromagnetism) biology.protein |
| Zdroj: | Cell. 143(6):911-923 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2010.11.029 |
| Popis: | Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR -/- pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR -/- epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR -/- pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. © 2010 Elsevier Inc. published_or_final_version |
| Databáze: | OpenAIRE |
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