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ACTION MECHANISMS OF HMG-1 ON ENDOTOXIN SHOCK

Research Project

Project/Area Number 13670282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKITASATO UNIVERSITY

Principal Investigator

HASUNUMA Ryoichi  KITASATO UNIV., SCHOOL OF SCIENCE, ASSISTANT PROFESSOR, 理学部, 助手 (30104566)

Co-Investigator(Kenkyū-buntansha) KUMAZAWA Yoshio  KITASATO UNIV., SCHOOL OF SCIENCE, PROFESSOR, 理学部, 教授 (30072375)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsHMG-1 / ENDOTOXIN SHOCK / GALACTOSAMINE-SENSITIZED MODEL / APOPTOSIS / ネズミチフス菌感染
Research Abstract

(1) The clearance and activity of different types of lipopolysaccharide (LPS) released during infection with gram-negative bacteria were investigated. When highly purified preparations were administered intravenously to mice, the clearance of rough-form LPS preparations much faster than that of a smooth-form LPS. After intraperitoneal infection with 10^8 CFU E.coli O111 : B4, relatively high levels of LPS were detected in the plasma of infected mice and persisted for a long time. These results indicate that continuously higher levels of plasma LPS followed by stronger host responses occur during infection and suggest that these differences between LPS-administered and infected mice should be taken into consideration when analyzing host responses induced by LPS.
(2) In a novel model for endotoxin shock that was caused by intraperitoneal infection with 10^8 CFU of attenuated Salmonella typhimurium, therapeutic effects of fosfomycin (FOF) and imipenem (IPM) were investigated. Treatment wit … More h FOF 1 h postinfection resulted in significant decreases in bacterial numbers in spleen and liver, suggesting that the antimicrobial activity of FOF seems to closely correlate to suppression of infection-induced lethal shock.
(3) The role of HMG-1 in LPS- and TNF-α-induced lethal shock in galactosamine (GalN)-sensitized mice was investigated. When GalN-sensitized mice were injected with TNF-α, HMG-1 was seen at 5.5 h in plasma of BALB/c mice and at 6 h in BALB/lps^d mice, although almost GalN-sensitized BALB/c mice died by 6 h after challenge. The time-dependent phenomenon correlated with elevated serum aspartate aminotransferase levels and the appearance of apoptotic cells in livers. Administration of pooled plasma, equivalent to approximately 200 μg recombinant murine HMG-1, taken from mice on the verge of near death, did not result in induction of lethal shock in GalN-sensitized mice. Taken together with the late appearance of HMG-1 in moribund mice, these data suggest that HMG-1 does not decisively contribute to lethality in the GalN sensitization model. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Hasunuma R., H.Morita, S.Tanaka, R.Ryll et al.: "Differential clearance of and induction of host responses by various administered or released lipopolysaccharides"J. Endotoxin Res.. 7・6. 421-429 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawaguchi K., R.Hasunuma, S.Kikuchi, R.Ryll, et al.: "Time and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice"Biol. Pharm. Bull.. 25・12. 1658-1661 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasunuma R., H.Maruyama H.Takimoto, R.Ryll et al.: "Dose High Mobility Group 1 Protein function as a late mediator for LPS-or TNF-induced shock in galactosamine-sensitized mice?"J. Endotoxin Res.. 8・5. 391-398 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasunuma R, Morita H, Tanaka S, Ryll R, Freudenberg MA, Galanos C, Kumazawa Y: "Differential clearance and induction of host responses by various administered or released lipopolysaccharides"J Endotoxin Res. 7(6). 421-429 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawaguchi K, Hasunuma R, Kikuchi S, Ryll R, Morikawa K, KumazawaY: "Time- and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice"Biol Pharm Bull. 25(12). 1658-1661 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasunuma R, Maruyama H, Takimoto H, Ryll R, Tanaka S, Kumazawa Y: "Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice?"J Endotoxin Res. 8(5). 391-398 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasunuma R., H.Maruyama, H.Takimoto, R.Ryll et al.: "Does High Mobility Group 1 Protein function as a late mediator for LPS-or TNF-induced shock in galactosamine-sensitized mice?"Jornal of Endotoxin Research. 8・5. 391-398 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawaguchi K., R.Hasunuma, S.Kikuchi, R.Ryll, et al.: "Time and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice"Biol. Pharm. Bull. 25・12. 1653-1656 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Hasunuma, H.Morita, S.Tanaka, R.Ryll, M.A.Freudenberg et al.: "Differential clearance and induction of host responses by various administered or released lipopolysaccharides"Jornal of Endotoxin Research. 7・6. 421-429 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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