Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: relevance to infections in cystic fibrosis

Magon, Nicholas J., Turner, Rufus, Gearry, Richard B., Hampton, Mark B., Sly, Peter D. and Kettle, Anthony J. (2015) Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: relevance to infections in cystic fibrosis. Free Radical Biology and Medicine, 86 133-144. doi:10.1016/j.freeradbiomed.2015.05.022

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ396566_OA.pdf Full text (open access) application/pdf 1.36MB 0

Author Magon, Nicholas J.
Turner, Rufus
Gearry, Richard B.
Hampton, Mark B.
Sly, Peter D.
Kettle, Anthony J.
Title Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: relevance to infections in cystic fibrosis
Journal name Free Radical Biology and Medicine   Check publisher's open access policy
ISSN 0891-5849
1873-4596
Publication date 2015-09
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.freeradbiomed.2015.05.022
Open Access Status File (Author Post-print)
Volume 86
Start page 133
End page 144
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundant in the lungs of patients with cystic fibrosis but fails to prevent their recurrent infections. Calprotectin is a major protein of neutrophils and composed of two monomers, S100A8 and S100A9. We show that the ability of calprotectin to limit growth of Staphylococcus aureus and Pseudomonas aeruginosa is exquisitely sensitive to oxidation by hypochlorous acid. The N-terminal cysteine residue on S100A9 was highly susceptible to oxidation which resulted in cross-linking of the protein monomers. The N-terminal methionine of S100A8 was also readily oxidized by hypochlorous acid, forming both the methionine sulfoxide and the unique product dehydromethionine. Isolated human neutrophils formed these modifications on calprotectin when their myeloperoxidase generated hypochlorous acid. Up to 90% of the N-terminal amine on S100A8 in bronchoalveolar lavage fluid from young children with cystic fibrosis was oxidized. Oxidized calprotectin was higher in children with cystic fibrosis compared to disease controls, and further elevated in those patients with infections. Our data suggest that oxidative stress associated with inflammation in cystic fibrosis will stop metal sequestration by calprotectin. Consequently, strategies aimed at blocking extracellular myeloperoxidase activity should enable calprotectin to provide nutritional immunity within the airways.
Keyword Calprotectin
Methionine
Dehydromethionine
Methionine sulfoxide
S100A8
S100A9
Hypochlorous add
Nutritional immunity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 19 Jul 2016, 16:35:23 EST by Anthony Yeates on behalf of Learning and Research Services (UQ Library)