論文

査読有り
2016年7月

Histidine-Rich Glycoprotein Prevents Septic Lethality through Regulation of Immunothrombosis and Inflammation

EBIOMEDICINE
  • Hidenori Wake
  • ,
  • Shuji Mori
  • ,
  • Keyue Liu
  • ,
  • Yuta Morioka
  • ,
  • Kiyoshi Teshigawara
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Kosuke Kuroda
  • ,
  • Yuan Gao
  • ,
  • Hideo Takahashi
  • ,
  • Aiji Ohtsuka
  • ,
  • Tadashi Yoshino
  • ,
  • Hiroshi Morimatsu
  • ,
  • Masahiro Nishibori

9
開始ページ
180
終了ページ
194
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ebiom.2016.06.003
出版者・発行元
ELSEVIER SCIENCE BV

Sepsis is a major cause of death worldwide. We show that a plasma protein histidine-rich glycoprotein (HRG) was decreased significantly in septic mice with cecal ligation and puncture (CLP) and supplementary treatment of septic mice with exogenous HRG improved survival, with strong inhibition of tight attachment of neutrophils to pulmonary vasculatures, subsequent immunothrombosis, DIC state, lung inflammation, hypercytokinemia, and activation of vascular endothelial cells (VECs). In contrast, knockdown of HRG by siRNA exacerbated lethality. Purified human HRG reversibly induced morphological changes in human neutrophils in vitro; induction of spherical shape with reduced microvilli and adhesiveness to VECs. HRG maintained the passage of neutrophils through microcapillaries and abolished production of reactive oxygen species. These results suggested that the supplementary therapy with HRG may provide a novel strategy for the treatment of sepsis through suppression of excessive systemic inflammation and immunothrombosis by keeping circulating neutrophils quiescent and preventing uncontrolled activation of VECs. (C) 2016 The Authors. Published by Elsevier B.V.

Web of Science ® 被引用回数 : 34

リンク情報
DOI
https://doi.org/10.1016/j.ebiom.2016.06.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27333033
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000381622500030&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.ebiom.2016.06.003
  • ISSN : 2352-3964
  • PubMed ID : 27333033
  • Web of Science ID : WOS:000381622500030

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