HOCl forms lipid N-chloramines in cell membranes of bacteria and immune cells

Neutrophils orchestrate a coordinated attack on bacteria, combining phagocytosis with a potent cocktail of oxidants, including the highly toxic hypochlorous acid (HOCl), renowned for its deleterious effects on proteins. Here, we examined the occurrence of lipid N-chloramines in vivo, their biologica...

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Bibliographic Details
Published in:Free radical biology & medicine Vol. 224; pp. 588 - 599
Main Authors: Knoke, Lisa R., Herrera, Sara Abad, Heinrich, Sascha, Peeters, Frank M.L., Lupilov, Natalie, Bandow, Julia E., Pomorski, Thomas Günther
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-11-2024
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Summary:Neutrophils orchestrate a coordinated attack on bacteria, combining phagocytosis with a potent cocktail of oxidants, including the highly toxic hypochlorous acid (HOCl), renowned for its deleterious effects on proteins. Here, we examined the occurrence of lipid N-chloramines in vivo, their biological activity, and their neutralization. Using a chemical probe for N-chloramines, we demonstrate their formation in the membranes of bacteria and monocytic cells exposed to physiologically relevant concentrations of HOCl. N-chlorinated model membranes composed of phosphatidylethanolamine, the major membrane lipid in Escherichia coli and an important component of eukaryotic membranes, exhibited oxidative activity towards the redox-sensitive protein roGFP2, suggesting a role for lipid N-chloramines in protein oxidation. Conversely, glutathione a cellular antioxidant neutralized lipid N-chloramines by removing the chlorine moiety. In line with that, N-chloramine stability was drastically decreased in bacterial cells compared to model membranes. We propose that lipid N-chloramines, like protein N-chloramines, are involved in inflammation and accelerate the host immune response. [Display omitted] •HOCl forms lipid N-chloramines in bacterial and mammalian membranes.•Lipid N-chloramines oxidize protein thiols.•Stability of N-chloramines is drastically reduced in vivo compared to model membranes.
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ISSN:0891-5849
1873-4596
1873-4596
DOI:10.1016/j.freeradbiomed.2024.09.014