Figure 8. Mechanisms of Sepsis and Histone-induced Cell and Tissue Damage after Polymicrobial Sepsis.

Infectious sepsis triggers complement activation and appearance of extracellular histones. Histones generally bind to TLR2 and TLR4 on a variety of cell types, resulting in activation of platelets, PMNs and macrophages. Histones can also directly cause cell dysfunction and apoptosis. Collectively, extracellular histones have strong prothrombotic and proinflammatory activities.