Histone proteins at histone–DNA interfaces (Histone–DNA interface)

Histone proteins at the histone–DNA interface within immune cells, particularly neutrophils, represent a critical structural and functional complex involved in the innate immune response. During a process known as NETosis, these proteins are released into the extracellular space as part of Neutrophil Extracellular Traps (NETs), where they serve to capture and neutralize pathogens [1]. However, when present in the extracellular environment, these histones act as potent damage-associated molecular patterns (DAMPs) that can cause significant endothelial damage and organ dysfunction [2]. The histone–DNA interface is specifically targeted by therapeutic agents to mitigate the cytotoxic effects of these proteins in conditions such as sepsis and systemic inflammation [3]. For instance, monoclonal antibodies like mBv11 have been developed to bind this interface, thereby neutralizing histone toxicity without disrupting essential nuclear functions [4]. Additionally, polyanionic compounds like heparin can bind to the basic residues of histones at this interface, preventing their interaction with host cell membranes and subsequent lysis [5]. Understanding and targeting this specific interface is a burgeoning area of research for treating acute inflammatory disorders and autoimmune diseases.

Other names

Extracellular histonesNET-associated histonesNucleosomal histonesCell-free nucleosomesHistone-DNA complex

Neutralization of histone-mediated cytotoxicity, disruption of Neutrophil Extracellular Traps (NETs), inhibition of histone-induced platelet aggregation, and prevention of histone-mediated endothelial damage.