Endotoxin inactivation by endotoxin binding proteins : Significance in severe liver disturbances

内毒素结合蛋白灭活内毒素：在严重肝脏疾病中的意义

基本信息

批准号：
06670578
负责人：
FUKUI Hiroshi
金额：
$ 1.02万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670578/
关键词：
endotoxin albumin high density lipoprotein (HDL)alcohol acute hepatic failure tumor necrosis factor (TNF)トランスフェリン TNF-α IL-6 G-CSF

项目摘要

Significance of endotoxin (Et) binding proteins in severe liver disturbance was investigated in clinical and experimental studies. Clinical studies : In the present study, we confirmed that serum albumin has Et binding and Et inactivating actions. There was a decrease in Et inactivating rate (EIR) in terminal liver cirrhosis. EIR was positively correlated to serum HDL-cholesterol level and Et binding capacity of albumin and negatively correlated to Et binding capacity of transferrin in liver cirrhosis. In patients with advanced cirrhosis, plasma interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF) -alpha levels were increased, which was related to decreased Et binding capacity of albumin. These data suggested that decreased Et inactivation by albumin may lead to augmentatin of endotoxicity and elevations of the above cytokines. Experimental studies : The hepatic production of Et binding protein was increased when the Kupffer cells were preincubated in the medium containing ethanol and the resultant culture supernatant was added to the hepatocyte culture system. The amount of Et binding protein produced by the hepatocytes was increased as the ethanol concentration in the culture medium of Kupffer cells was increased. This endotoxin binding protein was proved to enhance the uptake of endotoxin and to suppress the production of TNF by the Kupffer cells. In acute ethanol-loaded rats, albumin-bound and highdensity lipoprotein (HDL) -bound Et was markedly increased. In chronic ethanolloaded rats, HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5g/kg bw of ethanol load, blood TNF and ALT levels were increased, when the HDL-bound Et was not further increased. In vitro study revealed that albumin and HDL inhibited Et uptake and TNF production by Kupffer cells. These data suggest that albumin and HDL may act as Et binding proteins and attenuate endotoxicity in alcoholics.

在临床和实验研究中研究了内毒素（ET）结合蛋白在严重肝脏障碍中的重要性。临床研究：在本研究中，我们证实血清白蛋白具有ET结合和ET失活作用。末端肝肝硬化中的ET灭活率（EIR）降低。 EIR与血清HDL-胆固醇水平和ET结合能力呈正相关，并且与肝肝硬化中转铁蛋白的ET结合能力负相关。在晚期肝硬化的患者中，血浆白介素（IL）-1BETA，IL -6和肿瘤坏死因子（TNF） - α水平升高，这与白蛋白的ET结合能力降低有关。这些数据表明，白蛋白降低ET灭活可能会导致内毒素的增强和上述细胞因子的升高。实验研究：将Kupffer细胞在含有乙醇的培养基中预孵育时增加ET结合蛋白的肝产生，并将所得培养的上清液添加到肝细胞培养系统中。随着kupffer细胞培养基中的乙醇浓度的增加，肝细胞产生的ET结合蛋白量增加。事实证明，这种内毒素结合蛋白可增强内毒素的摄取并抑制库普弗细胞的TNF产生。在急性乙醇的大鼠中，白蛋白结合和高密度脂蛋白（HDL） - 结合蛋白ET显着增加。在慢性乙醇载体大鼠中，HDL结合的ET增加了。在慢性乙醇喂养的大鼠中，当HDL结合的ET没有进一步增加时，血液TNF和ALT水平增加了5g/kg BW。体外研究表明，白蛋白和HDL抑制了Kupffer细胞的ET摄取和TNF产生。这些数据表明，白蛋白和HDL可以充当ET结合蛋白，并减弱酒精中毒的内毒素。