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Investigation of heterogeneity of tissue macrophages and inflammatory immune response during infection.

Research Project

Project/Area Number 15591394
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionUniversity of Yamanashi

Principal Investigator

KONO Hiroshi  University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Research Associate, 大学院・医学工学総合研究部, 助手 (40322127)

Co-Investigator(Kenkyū-buntansha) MATSUDA Masanori  University of Yamanashi, University of Yamanashi Hospital, Lecturer, 医学部附属病院, 講師 (80242642)
AMEMIYA Hidetake  University of Yamanashi, University of Yamanashi Hospital, Medical Official, 医学部附属病院, 医員 (70377547)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsKupffer cell / acute lung injury / peritonitis / endotoxin / cytokine / chemokine
Research Abstract

The role of Kupffer cells (KCs) in acute lung injury was investigated in two different inflammatory models, peritonitis and endotoxin bolus infusion models, in rats. Furthermore, phenotypic and functional differences in KCs and tissue macrophages (Mφs) were also investigated. Rats were given GdCl_3 24 hours prior to LPS administration, and survival rate was assessed for 24 hours. In another set of experiments, rats were given saline or gadolinium chloride (GdCl_3), a KC toxicant, 24 hours before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. GdCl_3 completely prevented increases in lung microvascular permeability and mortality after LPS bolus infusion. On the other hand, GdCl_3 treatment increased lung injury and reduced the survival rate. Furthermore, from phenotypic analysis, KCs were divided into 3 subpopulations based on size and phagocytosis. Moreover, functional differences were observed in response of tissue Mφs to endotoxin. Thus, the heterogeneous response of KCs and tissue Mφs to endotoxin leads to production of certain cytokines and chemokines that affect lung function. Furthermore, the role of KCs in acute lung injury depends on pathophysiological condition during inflammation.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (7 results)

All 2004 2003 Other

All Journal Article (5 results) Publications (2 results)

  • [Journal Article] Medium-chain triglycerides modulate inflammatory immune response in the gut in rats administered endotoxin.2004

    • Author(s)
      Kono H et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Medium-chain triglycerides modulate inflammatory immune response in the gut in rats administered endotoxin.2004

    • Author(s)
      Kono H et al.
    • Journal Title

      American Journal of Physiology 286

      Pages: 1081-1089

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin.2003

    • Author(s)
      Kono H et al.
    • Journal Title

      J Pharmacol Exp Ther 307

      Pages: 74-82

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protective effects of medium-chain triglycerides on the liver and the gut in rats administered endotoxin.2003

    • Author(s)
      Kono H et al.
    • Journal Title

      Ann Surg 237

      Pages: 246-255

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin.2003

    • Author(s)
      Kono H et al.
    • Journal Title

      J Pharmacol Exp Ther 307(1)

      Pages: 74-82

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kono H et al.: "Medium-chain triglycerides modulate inflammatory immune response in the gut in rats administered endotoxin"American Journal of Physiology. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kono H et al.: "Edaravone, a Novel Free Radical Scavenger, Prevents Liver Injury and Mortality in Rats Administered Endotoxin"Journal of Pharmacology and Experimental Therapeutics. 307. 74-82 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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