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Abstract

Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Extracellular histones are considered to be the main cause of septic death because of their cytotoxic effect on endothelial cells, which makes them a potential therapeutic target. We found that PTX3 interacted with histones to form coaggregates, which depended on polyvalent interactions and disorder in the secondary structure of PTX3. PTX3 exerted a protective effect, both in vitro and in vivo, against histone-mediated cytotoxicity toward endothelial cells. Additionally, the intraperitoneal administration of PTX3 reduced mortality in mouse models of sepsis. The amino-terminal domain of PTX3, which was required for coaggregation with histones, was sufficient to protect against cytotoxicity. Our results suggest that the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. This long pentraxin–specific effect provides a potential basis for the treatment of sepsis directed at protecting cells from the toxic effects of extracellular histones.UTokyo Research掲載「ペントラキシン3の敗血症への効果を発見」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/host-protective-effect-of-pentraxin-3-in-sepsis/

UTokyo Research "Host-protective effect of pentraxin 3 in sepsis" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/host-protective-effect-of-pentraxin-3-in-sepsis/

Journal

  • Science signaling

    Science signaling 7(343), ra88, 2014-09-16

    American Association for the Advancement of Science

Codes

  • NII Article ID (NAID)
    120005537769
  • NII NACSIS-CAT ID (NCID)
    AA12315525
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1945-0877
  • Data Source
    IR 
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