title: The lactoperoxidase system links anion transport to host defense in cystic fibrosis.
abstract: Chronic respiratory infections in cystic fibrosis result from CFTR channel mutations but how these impair antibacterial defense is less clear. Airway host defense depends on lactoperoxidase (LPO) that requires thiocyanate (SCN-) to function and epithelia use CFTR to concentrate SCN- at the apical surface. To test whether CFTR mutations result in impaired LPO-mediated host defense, CF epithelial SCN- transport was measured. CF epithelia had significantly lower transport rates and did not accumulate SCN- in the apical compartment. The lower CF [SCN-] did not support LPO antibacterial activity. Modeling of airway LPO activity suggested that reduced transport impairs LPO-mediated defense and cannot be compensated by LPO or H2O2 upregulation.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, FL 33136, United States. gconner@miami.edu
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Conner
authors.forename: Corinne
authors.initials: C
authors.lastname: Wijkstrom-Frei
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.forename: Vania E
authors.initials: VE
authors.lastname: Fernandez
authors.forename: Matthias
authors.initials: M
authors.lastname: Salathe
mesh_terms: D000838:Anions / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004847:Epithelial Cells / Q000201:enzymology / Q000382:microbiology; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D007784:Lactoperoxidase / Q000032:analysis / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000382:microbiology; D008954:Models, Biological; D011550:Pseudomonas aeruginosa; D013861:Thiocyanates / Q000378:metabolism*
chemical_list: D000838:Anions; D013861:Thiocyanates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007784:Lactoperoxidase; C031760:thiocyanate