1. Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia
- Author
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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, and Joseph Zabner
- Subjects
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 - Abstract
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
- Published
- 2010
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