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

通过调节 PBMC 上内毒素受体（TLR4、RP105）的表达预防多器官功能障碍综合征

• 批准号: 15591925
• 负责人: HIROHASHI Nobuyuki
• 金额: $ 1.09万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591925/
• 关键词: Endotoxin; TLR4; RP105; Cytokine; MOF

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.

TLR 4是一种富含亮氨酸的重复序列（Leucine-rich repeat，LRR）分子，可识别LPS并发出信号。RP 105是另一种LRR分子，可以感知病原体入侵并激活B细胞。在本研究中，我们分析了SIRS/SEPSIS患者PBMC表面TLR 4和RP 105的表达。应用单克隆抗体和流式细胞术分析SIRS/SPSIS患者PBMC上TLR 4、RP 105和各种标志物的表达。在单核细胞中，所有CD 11b或CD 14阳性细胞均为TLR 4或RP 105阳性。在淋巴细胞中，来自正常或SIRS/SEPSIS患者的受试者的所有CD 3阳性细胞均为TLR 4和RP 105阴性。正常受试者的所有CD 19阳性细胞均为RP 105阳性，SIRS/SEPSIS患者的CD 19阳性细胞含有大量RP 105阴性B细胞。RP 105阴性B细胞数与血清内毒素浓度无相关性，但与SIRS评分和SOFA评分有相关性。提示RP 105阴性B细胞在SIRS/SEPSIS中可能起重要作用。SIRS/SEPSIS时单核细胞TLR 4和RP 105表达下调。血浆中巨噬细胞移动抑制因子（macrophagemigrationinhibitoryfactor，MIF）浓度与其它急性时相分子IL-6/IL-10浓度之间存在相关性。SIRS/SEPSIS晚期分子HMBG 1（high mobility group box 1）与MIF浓度也存在相关性。但单核细胞TLR 4/RP 105的表达与血浆中MIF/HMG 1的浓度无相关性。