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Organ distribution of histones after intravenous infusion of FITC histones or after sepsis

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Abstract

Histones appear in plasma during infectious or non-infectious sepsis and are associated with multiorgan injury. In the current studies, intravenous infusion of histones resulted in their localization in major organs. In vitro exposure of mouse macrophages to histones caused a buildup of histones on cell membranes followed by localization into cytosol and into the nucleus. After polymicrobial sepsis (cecal ligation and puncture), histones appeared in plasma as well as in a multiorgan pattern, peaking at 8 h followed by decline. In lungs, histones and neutrophils appeared together, with evidence for formation of neutrophil extracellular traps (NETs), which represent an innate immune response to trap and kill bacteria and other infectious agents. In liver, there was intense NET formation, featuring linear patterns containing histones and strands of DNA. When neutrophils were activated in vitro with C5a or phorbol myristate acetate, NET formation ensued. While formation of NETs represents entrapment and killing of infectious agents, the simultaneous release from neutrophils of histones often results in tissue/organ damage.

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Acknowledgments

This work was supported by grants from the National Institutes of Health, GM-29507 and GM-61656 (PAW). The authors are responsible for the scientific content of this publication. The authors declare no commercial or financial conflicts of interests. We also acknowledge the expert assistance of Sue Scott and Melissa Rennells with the manuscript preparation.

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    1. Department of Pathology, University of Michigan Medical School, 7520 MSRB I, 1301 Catherine Rd, Ann Arbor, MI, 48109-5602, USA

      Fatemeh Fattahi, Jamison J. Grailer, Lawrence Jajou, Firas S. Zetoune, Anuska V. Andjelkovic & Peter A. Ward

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    1. Fatemeh Fattahi
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    2. Jamison J. Grailer
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    Correspondence to Peter A. Ward.

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    Fatemeh Fattahi and Jamison J. Grailer have contributed equally to this work.

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    Fattahi, F., Grailer, J.J., Jajou, L. et al. Organ distribution of histones after intravenous infusion of FITC histones or after sepsis. Immunol Res 61, 177–186 (2015). https://doi.org/10.1007/s12026-015-8628-2

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