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Sepsis: the dark side of histones

Nature Medicine volume 15, pages 1245–1246 (2009)Cite this article

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.

Histones are not generally considered to be noxious; after all, they form the core around which DNA is wrapped in eukaryotes. Not only do these proteins have this essential architectural role, but also their modification is one of the key mechanisms for gene regulation. Although initially described in 1958 (ref. 1), it is not widely known that histones possess an additional startling capacity: they are able to kill. James G. Hirsch and, later, many others showed that histones kill microbes more potently than do canonical antimicrobials. Now, in this issue of Nature Medicine, Xu et al.2 show that histones also kill human cells, with devastating effects.

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Figure 1: Far from harmless histones.

Marina Corral

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Affiliations

  1. Catherine Chaput and Arturo Zychlinsky are in the Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.

    Catherine Chaput & Arturo Zychlinsky

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  1. Catherine Chaput
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  2. Arturo Zychlinsky
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Correspondence to Arturo Zychlinsky.

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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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