L.R. Knoke, S.A. Herrera, S. Heinrich, N. Lupilov, J.E. Bandow and T. Günther Pomorski (2024).
HOCl forms lipid N-chloramines in cell membranes of bacteria and immune cells.
Free Radical Biology and Medicine
doi: 10.1101/2024.06.25.600395
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.