N-chlorination mediates protective and immunomodulatory effects of oxidized human plasma proteins

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Cite this article as: eLife 2019;8:e47395 doi: 10.7554/eLife.47395

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Abstract

Hypochlorous acid (HOCl), a powerful antimicrobial oxidant, is produced by neutrophils to fight infections. Here we show that N-chlorination, induced by HOCl concentrations encountered at sites of inflammation, converts blood plasma proteins into chaperone-like holdases that protect other proteins from aggregation. This chaperone-like conversion was reversible by antioxidants and was abrogated by prior methylation of basic amino acids. Furthermore, reversible N-chlorination of basic amino acid side chains is the major factor that converts plasma proteins into efficient activators of immune cells. Finally, HOCl-modified serum albumin was found to act as a pro-survival molecule that protects neutrophils from cell death induced by highly immunogenic foreign antigens. We propose that activation and enhanced persistence of neutrophils mediated by HOCl-modified plasma proteins, resulting in the increased and prolonged generation of ROS, including HOCl, constitutes a potentially detrimental positive feedback loop that can only be attenuated through the reversible nature of the modification involved.

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Agnes Ulfig

Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Anton V Schulz

Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Alexandra Müller

Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Natalie Lupilov

Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Lars I Leichert

Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum, Bochum, Germany

For correspondence
lars.leichert@ruhr-uni-bochum.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5666-9681

Funding

Deutsche Forschungsgemeinschaft (LE2905/1-2)

Lars I Leichert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

Jos WM van der Meer, Radboud University Medical Centre, Netherlands

Publication history

Received: April 3, 2019
Accepted: July 11, 2019
Accepted Manuscript published: July 12, 2019 (version 1)
Version of Record published: July 23, 2019 (version 2)

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.