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タイトル: Protective effect of the long pentraxin PTX3 against histone-mediated endothelial cell cytotoxicity in sepsis
著者: Daigo, Kenji
Nakakido, Makoto
Ohashi, Riuko
Fukuda, Rie
Matsubara, Koichi
Minami, Takashi
Yamaguchi, Naotaka
Inoue, Kenji
Jiang, Shuying
Naito, Makoto
Tsumoto, Kouhei
Hamakubo, Takao
発行日: 2014年9月16日
出版者: American Association for the Advancement of Science
掲載誌情報: Science Signaling, Vol. 7, Issue 343, ra88, DOI: 10.1126/scisignal.2005522 (2014).
関連URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/host-protective-effect-of-pentraxin-3-in-sepsis/
抄録: 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.
内容記述: 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/
URI: http://hdl.handle.net/2261/56112
ISSN: 1945-0877 (print)
1937-9145 (online)
出現カテゴリ:014 自然科学
14010 学術雑誌論文


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