PT  - JOURNAL ARTICLE
AU  - Agnes Ulfig
AU  - Anton V. Schulz
AU  - Alexandra Müller
AU  - Natalie Lupilov
AU  - Lars I. Leichert
TI  - <em>N</em>-chlorination mediates protective and immunomodulatory effects of oxidized human plasma proteins
AID  - 10.1101/584961
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 584961
4099  - http://biorxiv.org/content/early/2019/04/11/584961.short
4100  - http://biorxiv.org/content/early/2019/04/11/584961.full
AB  - 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.