Injection of activated protein C (APC) is the last resort to rescue a patient with severe sepsis. Research into how APC works reveals that the drug inactivates histones (pages 1318–1321), which are toxic during severe sepsis.
References
Hirsch, J.G. J. Exp. Med. 108, 925–944 (1958).
Xu, J. et al. Nat. Med. 15, 1318–1321 (2009).
Kerschen, E.J. et al. J. Exp. Med. 204, 2439–2448 (2007).
Wang, H.G. et al. Science 284, 339–343 (1999).
Clark, S.R. et al. Nat. Med. 13, 463–469 (2007).
Brinkmann, V. et al. Science 303, 1532–1535 (2004).
Hamon, M.A. & Cossart, P. Cell Host Microbe 4, 100–109 (2008).
Malik, H.S. & Henikoff, S. Nat. Struct. Biol. 10, 882–891 (2003).
Jaeger, S. et al. Biochimie 87, 827–834 (2005).
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Chaput, C., Zychlinsky, A. Sepsis: the dark side of histones. Nat Med 15, 1245–1246 (2009). https://doi.org/10.1038/nm1109-1245
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DOI: https://doi.org/10.1038/nm1109-1245
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