ACTION MECHANISMS OF HMG-1 ON ENDOTOXIN SHOCK

HMG-1抗内毒素休克的作用机制

• 批准号: 13670282
• 负责人: HASUNUMA Ryoichi
• 金额: $ 1.98万
• 依托单位: KITASATO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670282/
• 关键词: HMG-1; ENDOTOXIN SHOCK; GALACTOSAMINE-SENSITIZED MODEL; APOPTOSIS; ネズミチフス菌感染

(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

(1)研究了革兰阴性菌感染时释放的不同类型脂多糖（LPS）的清除和活性。当将高度纯化的制剂静脉内给予小鼠时，粗糙形式的LPS制剂的清除比光滑形式的LPS快得多。腹腔感染10^8 CFU大肠杆菌O 111：B4后，在感染小鼠血浆中检测到相对高水平的LPS，并持续较长时间。这些结果表明，持续更高水平的血浆LPS，随后更强的宿主反应发生在感染过程中，并建议LPS管理和感染的小鼠之间的这些差异应考虑到当分析LPS诱导的宿主反应。(2)在腹腔感染10^8 CFU减毒鼠伤寒沙门氏菌引起内毒素休克的新模型中，研究了磷霉素（FOF）和亚胺培南（IPM）的治疗作用。治疗智慧 ...更多信息 h感染后1 h，脾脏和肝脏中的细菌数量显著减少，表明FOF的抗菌活性似乎与抑制感染诱导的致死性休克密切相关。(3)用半乳糖胺（GalN）致敏小鼠，观察HMG-1在LPS和TNF-α诱导的致死性休克中的作用。当GalN致敏的小鼠注射TNF-α时，HMG-1在BALB/c小鼠的血浆中于5.5h和在BALB/lps^d小鼠的血浆中于6 h出现，尽管GalN致敏的BALB/c小鼠在攻击后6 h几乎死亡。时间依赖性现象与血清天冬氨酸转氨酶水平升高和肝脏中凋亡细胞的出现相关。从濒临死亡的小鼠中采集的相当于约200 μg重组鼠HMG-1的合并血浆的给药在GalN致敏小鼠中未导致致死性休克的诱导。结合濒死小鼠中HMG-1的晚期出现，这些数据表明HMG-1在GalN致敏模型中并不决定性地导致致死性。少

项目成果

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)

Hasunuma R.、H.Morita、S.Tanaka、R.Ryll 等：“不同施用或释放的脂多糖对宿主反应的差异清除和诱导”J. 7・6（2001 年）。 ）

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)

Hasunuma R、Maruyama H、Takimoto H、Ryll R、Tanaka S、Kumazawa Y：“高迁移率组 1 蛋白是否作为半乳糖胺致敏小鼠中 LPS 或 TNF 诱导休克的晚期介质发挥作用？”J Endotoxin Res。

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)

Hasunuma R.、H.Maruyama、H.Takimoto、R.Ryll 等人：“高迁移率组 1 蛋白是否作为半乳糖胺致敏小鼠中 LPS 或 TNF 诱导休克的晚期介质发挥作用？”内毒素研究杂志8・5。391-398（2002）

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)

Kawaguchi K.、R.Hasunuma、S.Kikuchi、R​​.Ryll 等：“磷霉素对小鼠感染引起的内毒素休克的抑制作用的时间和剂量依赖性”Biol 25・12。 1653-1656 (2002)

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)

Hasunuma R.、H.Maruyama H.Takimoto、R.Ryll 等人：“剂量高迁移率组 1 蛋白在半乳糖胺致敏小鼠中充当 LPS 或 TNF 诱导休克的晚期介质？”J. Endotoxin Res。 8・5。391-398（2002）