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HOCl Forms Lipid N-Chloramines in Cell Membranes of Bacteria and Immune Cells

Knoke, L. R.; Abad Herrera, S.; Heinrich, S.; Lupilov, N.; Bandow, J. E.; Gunther Pomorski, T.

2024-06-25 microbiology
10.1101/2024.06.25.600395 bioRxiv
Show abstract

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 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, the cellular antioxidant glutathione neutralized lipid N-chloramines by removing the chlorine moiety. We propose that lipid N-chloramines, like protein N-chloramines, are involved in inflammation and accelerate the host immune response.

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