The lactoperoxidase system links anion transport to host defense in cystic fibrosis

Gregory E. Conner; Corinne Wijkstrom-Frei; Scott H. Randell; Vania E. Fernandez; Matthias Salathe

doi:10.1016/j.febslet.2006.12.025

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

Gregory E. Conner, Corinne Wijkstrom-Frei, Scott H. Randell, Vania E. Fernandez, Matthias Salathe

Cell Biology

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

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.

Original language	English (US)
Pages (from-to)	271-278
Number of pages	8
Journal	FEBS letters
Volume	581
Issue number	2
DOIs	https://doi.org/10.1016/j.febslet.2006.12.025
State	Published - Jan 23 2007

Keywords

CFTR
Cystic fibrosis
Host defense
Hydrogen peroxide
Lactoperoxidase
Thiocyanate

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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10.1016/j.febslet.2006.12.025

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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.",

keywords = "CFTR, Cystic fibrosis, Host defense, Hydrogen peroxide, Lactoperoxidase, Thiocyanate",

author = "Conner, {Gregory E.} and Corinne Wijkstrom-Frei and Randell, {Scott H.} and Fernandez, {Vania E.} and Matthias Salathe",

note = "Funding Information: We thank Dr. Adam Wanner for his thoughtful advice and strong support throughout this work. This work also acknowledges the memory of James R. Haft M.D. who inspired us by his lifelong determination and his dedication to medicine before his death from cystic fibrosis. This work was supported in part by the grants from NHLBI (G.E.C. and M.S.) and The Cystic Fibrosis Foundation (S.H.R.). Correspondence and requests for materials should be addressed to G.E.C.",

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doi = "10.1016/j.febslet.2006.12.025",

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AU - Conner, Gregory E.

AU - Wijkstrom-Frei, Corinne

AU - Randell, Scott H.

AU - Fernandez, Vania E.

AU - Salathe, Matthias

N1 - Funding Information: We thank Dr. Adam Wanner for his thoughtful advice and strong support throughout this work. This work also acknowledges the memory of James R. Haft M.D. who inspired us by his lifelong determination and his dedication to medicine before his death from cystic fibrosis. This work was supported in part by the grants from NHLBI (G.E.C. and M.S.) and The Cystic Fibrosis Foundation (S.H.R.). Correspondence and requests for materials should be addressed to G.E.C.

PY - 2007/1/23

Y1 - 2007/1/23

N2 - 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.

AB - 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.

KW - CFTR

KW - Cystic fibrosis

KW - Host defense

KW - Hydrogen peroxide

KW - Lactoperoxidase

KW - Thiocyanate

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The lactoperoxidase system links anion transport to host defense in cystic fibrosis

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Keywords

ASJC Scopus subject areas

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