Localization and regulation in reactive sites of DAMPs/PAMPs. Role of ATP from the activated plateles

• Project/Area Number: 25670764
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Emergency medicine
• Research Institution: Kagoshima University
• Principal Investigator: MARUYAMA Ikuro 鹿児島大学, 医歯(薬)学総合研究科, 特任教授 (20082282)
• Co-Investigator(Kenkyū-buntansha): ITO Takashi 鹿児島大学, 大学院医歯学総合研究科, 特任講師 (20381171)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: ATP / DAMP / PAMP / platelet / inflammation / PAMPｓ / DAMPｓ / ＡＴＰ / Ａｄｅｎｏｓｉｎｅ / Inflammasome / IL-1β / IL-18

Research Abstract

Dual signalings from PAMPs/DAMPs play crucial role in inflammation, immunity and hemostasis. It has been listed more than 1000 of molecules as PAMPs, and DAMPs each other.
In this study, we took LPS as PAMPs,and HMGB-1 and ATP as DAMPs, and stimulated macrophages or dendritic cells. We showed that dual signaling from LPS and HMGB1 or ATP stimulated the release of IL-1b(beta) and IL-18.Thus dual signaling plays crucial role in inflammation, immunity and hemostasis. It has been described that platelet contains inflammasome, however the role of platelet-inflammasome has been not known. We examined the role of platelet inflammasome. An inflammasome inhibitor,1,5-anhydrofructose inhibited platelets aggregation with decreased release of IL-1b(beta). Thus ATP from activated platelets might play important role for the hemostasis/inflammation.

Research Products

• [Journal Article] Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions : an in vitro flow chamber model (2014)
  • Author(s): Hosokawa K, Ohnishi T, Sameshima H, Miura N, Koide T, Maruyama I, Tanaka KA
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: 86491-86491
  • DOI: 10.1371/journal.pone.0086491
  • Peer Reviewed
• [Journal Article] Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions (2014)
  • Author(s): Hosokawa K, Ohnishi T, Miura N, Sameshima H, Koide T, Tanaka KA, Maruyama I
  • Journal Title: Thromb Res Volume: 133(1) Issue: 1 Pages: 66-72
  • DOI: 10.1016/j.thromres.2013.10.037
  • Peer Reviewed
• [Journal Article] Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism. (2013)
  • Author(s): Nakahara M, Ito T, et al.
  • Journal Title: PLoS One Volume: 8(9) Issue: 9 Pages: 75961-75961
  • DOI: 10.1371/journal.pone.0075961
  • Peer Reviewed
• [Journal Article] Saturated fatty acid palmitate induces extracellular release of histone H3 : a Possible mechanistic basis for high-fat diet-induced inflammation and thrombosis. (2013)
  • Author(s): Shrestha C, Ito T, et al.
  • Journal Title: Biochemical and biophysical research communications Volume: 437(4) Issue: 4 Pages: 573-578
  • DOI: 10.1016/j.bbrc.2013.06.117
  • Peer Reviewed
• [Presentation] Regulation of Danger Signals from HMGB1and Histones by Endothelial or Circulating Thrombomodulin (2013)
  • Author(s): Ikuro Maruyama
  • Organizer: The Merinoff World Congress 2013 : HMGB1
  • Place of Presentation: Manhasset, NY
• [Presentation] Assay method of des-HMGB1 (2013)
  • Author(s): Ikuro Maruyama, Takashi Ito, Yoshio Azuma, Mayumi Nakahara, Teruto Hashiguchi, Shingo Yamada
  • Organizer: N-terminus cleaved out HMGB1 by thrombin-thrombomodulin, and its clinical significance XXIVcongress of the ISTH
  • Place of Presentation: Amsterdam, The Netherlands