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Prevention of multiple organ dysfunction syndrome by modulation of the expression of endotoxin receptors (TLR4,RP105) on PBMC

Research Project

Project/Area Number 15591925
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionKurume University

Principal Investigator

HIROHASHI Nobuyuki  kurume University, School of Medicine, Department of Emergency and Critical Care Medicine, Assistant Professor, 医学部, 講師 (30218862)

Co-Investigator(Kenkyū-buntansha) TAKAMATSU Manabu  Kurume University, School of Medicine, Department of Emergency and Critical Care Medicine, Assistant professor, 医学部, 助手 (70352185)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsEndotoxin / TLR4 / RP105 / Cytokine / MOF
Research Abstract

TLR4, may recognize and signal LPS, is a leucine-rich repeat(LRR) molecule. RP105 is known as another LRR molecule that may sense pathogen invasion and activate B cells. In the present study, we analyzed the surface expression of TLR4 and RP105 on PBMC in SIRS/SEPSIS patients. The expression of TLR4,RP105 and various markers on PBMC in SIRS/SPSIS patients was analyzed using monoclonal antibodies and flowcytometry. In monocytes, all CD11b or CD14-positive cells were TLR4 or RP105 positive. In lymphocytes, all CD3-positive cells from the subject of the normal or the SIRS/SEPSIS patients, were TLR4 and RP105 negative. All CD19-positive cells from the normal subject were RP105 positive, those from the SIRS/SEPSIS patient contained a large number of RP105-negative B cells. There were no correlation between the cell numbers of RP105-negative B cells and serum endotoxin concentration, however there were correlation between the cell numbers of RP105-negative B cells and the score numbers of SIRS and SOFA. These findings suggested that RP105-negative B cells may play an important role in SIRS/SEPSIS. On the other hand, The expressions of TLR4 and RP105 on monocytes were down-regulated in SIRS/SEPSIS. There were correlation between the concentration of an acute phase molecule MIF(macrophage migration inhibitory factor) and those of other acute phase molecules IL-6/IL-10 in plasma. Interestingly, there were also correlation between the concentration of HMBG1(high mobility group box 1), the late phase molecule in SIRS/SEPSIS, and that of MIF. However there were no correlation between the expressions of TLR4/RP105 on monocytes and the concentrations of MIF/HMG1 in plasma.

Report

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

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

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