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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Kurume 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
• Keywords: Endotoxin / 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.