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Endotoxin inactivation by endotoxin binding proteins : Significance in severe liver disturbances

Research Project

Project/Area Number 06670578
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionNara Medical University

Principal Investigator

FUKUI Hiroshi  Nara Medical University, 3rd Dept of Internal Medicine, Professor, 医学部, 教授 (80145838)

Co-Investigator(Kenkyū-buntansha) UEMURA Masahito  Nara Medical University, 3rd Dept of Internal Medicine, Lecturer, 医学部, 講師 (90151836)
KIKUCHI Eiryou  Nara Medical University, 3rd Dept of Internal Medicine, Lecturer, 医学部, 講師 (50214747)
辻井 正  奈良県立医科大学, 医学部, 教授 (30075064)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Keywordsendotoxin / albumin / high density lipoprotein (HDL) / alcohol / acute hepatic failure / tumor necrosis factor (TNF) / トランスフェリン / TNF-α / IL-6 / G-CSF
Research Abstract

Significance of endotoxin (Et) binding proteins in severe liver disturbance was investigated in clinical and experimental studies. Clinical studies : In the present study, we confirmed that serum albumin has Et binding and Et inactivating actions. There was a decrease in Et inactivating rate (EIR) in terminal liver cirrhosis. EIR was positively correlated to serum HDL-cholesterol level and Et binding capacity of albumin and negatively correlated to Et binding capacity of transferrin in liver cirrhosis. In patients with advanced cirrhosis, plasma interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF) -alpha levels were increased, which was related to decreased Et binding capacity of albumin. These data suggested that decreased Et inactivation by albumin may lead to augmentatin of endotoxicity and elevations of the above cytokines. Experimental studies : The hepatic production of Et binding protein was increased when the Kupffer cells were preincubated in the medium containing ethanol and the resultant culture supernatant was added to the hepatocyte culture system. The amount of Et binding protein produced by the hepatocytes was increased as the ethanol concentration in the culture medium of Kupffer cells was increased. This endotoxin binding protein was proved to enhance the uptake of endotoxin and to suppress the production of TNF by the Kupffer cells. In acute ethanol-loaded rats, albumin-bound and highdensity lipoprotein (HDL) -bound Et was markedly increased. In chronic ethanolloaded rats, HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5g/kg bw of ethanol load, blood TNF and ALT levels were increased, when the HDL-bound Et was not further increased. In vitro study revealed that albumin and HDL inhibited Et uptake and TNF production by Kupffer cells. These data suggest that albumin and HDL may act as Et binding proteins and attenuate endotoxicity in alcoholics.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report

Research Products

(24 results)

All Other

All Publications (24 results)

  • [Publications] Fukui,H.et al: "Metabolic fate of endotoxin and blood tumour necrosis factaor levels in rats with acute and chronic alcohol loading" Alcohol Alcoholism. 28(SIA). 65-70 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui,H.et al: "Effect of aocohol on the functions of Kupffer cells and splenic macrophages in rats" Alcohol Alcoholism. 28(SIB). 53-57 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui,H et al: "Effect of alcohol on the endotoxin binding protein produced in the liver" Alcohol Alcoholism. 28(SI). 87-91 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui,H et al: "Endotoxin inactivating action of plasma in patients with liver cirrhosis" Liver. 15. 104-109 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui,H et al: "Interaction of Kupffer cells to splenic macrophages and hepatocytes in endotoxin clearance : effect of alcohol" J Gastroenterol Hepatol. 10. S31-S34 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kitano,H et al: "Roke of albumin and high-density lypoprotein as endotoxin bindig proteins in rats with acute and chronic alcohol loading" Alcoholism : Clinical and Experimental Research. 20. 73A-76A (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Kitano H,Morimura M,et al: "Metabolic fate of endotoxin and blood tumour necrosis factor levels in rats with acute and chronic alcohol loading" Alcohol Alcoholism. 28 (SIA). 65-70 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Kitano H,Tsujii T,et al: "Effect of alcohol on the functions of kupffer cells and splenic macrophages in rat" Alcohol Alcoholism. 28 (SIB). 53-57 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Matsumoto M,Tsujita S,et al: "Plasma endotoxin concentration and endotoxin binding capacity of plasma acute phase proteins in cirrhotics with variceal bleeding : an analysis by new methods" J Gastroenterol Hepatol. 9. 582-586 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Kitano H,Okamoto Y,et al: "Effect of alcohol on the endotoxin binding protein produced in the liver" Alcohol Alcoholism. 29 (S1). 87-91 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Tsujita S,Matsumoto M,et al: "Endotoxin inactivating action of plasma in patients with liver cirrhosis" Liver. 15. 104-109 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fukui H,Kitano H,Okamoto Y,et al: "Interaction of Kupffer cells to splenic macrophages and hepatocytes in endotoxin clearance : Effect of alcohol" J Gastroenterol Hepatol. 10. 31-34 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kitano H,Fukui H,Okamoto Y,et al: "Role of albumin and high-density lipoprotein as endotoxin-binding proteins in rats with acute and chronic alcohol loading" Alcoholism : Clinical and Experimental Research. 20. 73-76 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroyuki Kitano,et al.: "Role of albumin and high-density lipoprotein as endotoxin-binding proteins in rats with acute and chronic alcohol loading" Alcoholism:Clinical and Experimental Research. 20. 73A-76A (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Fukui,et al.: "Endotoxin inactivating action of plasmsa in patients with liver cirrhosis" Liver. 15. 104-109 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Fukui,et al.: "Effect of alcohol on the endotoxin binding protein produced in the liver" Alcohol & Alcoholism. 29,S1. 87-91 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Fukui,et al.: "Plasma endotoxin concentration and endotoxin binding capacity of plasma acute phase proteins in cirrhosis witle variceal bleeding" J Gastroenterol Hepatol. 9. 582-586 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Fukui,et al.: "Interaction of Kupffer cells to splenic macrophages and hepatocytes in endotoxin clearance effect of alcohol" J Gastroenterol Hepatol. 10. S31-S34 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Fukui et al: "Metabolic fate of endotoxin and blood tumor necrosis factor levels in rats with acute and chronic alcohol loading" Alcohol and alcoholism. 28(SIA). 65-70 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Fukui et al: "Effect of alcohol on the endotoxin binding protein production in the liver" Alcohol and alcoholism. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Fukui et al: "Endotoxin inactivating action of plasma in patients with liver cirrhosis" Liver. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] 福井 博ほか: "肝硬変における血中サイトカインとエンドトキシン" 消化器疾患とサイトカイン. 67-71 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 福井 博ほか: "肝硬変における血中エンドトキシン不活性化機構-Alubuminの意義を中心に" エンドトキシンシンポジウム講演記録集. 5. 110-114 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 福井 博ほか: "肝硬変における腹水中エンドトキシンとその病態生理学的意義" エンドトキシンシンポジウム講演記録集. 6. 34-36 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-03-31   Modified: 2016-04-21  

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