APC and Sepsis: Besides, After infusing of APC (activated protein C) with E. coli in baboons, they detected that histone in the circulation of baboons decreased and observed it could prevent lethality in mice, implying that APC could cleavage the histone (mainly H3 and H4), and the overactivation of NETs led to extracellular histones accumulation, thus contributed to the death of mice in sepsis (83).