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Animal model for severe alcoholic hepatitis by chronic ethanol feeding and immunization with fusions of dendritic cells and acetaldehyde adducts.

通过长期乙醇喂养和树突状细胞与乙醛加合物融合免疫来建立严重酒精性肝炎动物模型。

基本信息

批准号：
11670538
负责人：
SAITO Saburo
金额：
$ 2.24万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670538/
关键词：
Severe alcoholic hepatitis Acetaldehyde adduct Dendritic cells Alcoholic liver damage

项目摘要

(1) Mouse albumin-acetalciehyde adduct (ADT) was prepared with the reducing agent according to the method of Israel et al (Proc Nati Acad Sci USA 83 : 7923,1986).(2) In order to choose the mouse that responds to ADT well, four species of mice (B10S, BALB/C, C3H, and B6 mouse) with different strains were prepared. Mice were immunized with ADT. The lymphocytes were obtained from the systemic lymph node of each mouse, and in vitro lymphocyte stimulation test was performed. The stimulation index was remarkably higher in B6 mice than in any other mice.(3) B6 mice were divided into 6 groups with or without immunization and ethanol feeding (10 weeks). The stimulation index of ^3H-thymidine uptake into lymphocytes cultured with mouse albumin or ADT was measured, The stimulation .index was increased remarkably in ethanol-fed mice immunized with ADT. However, no elevation in plasma AST and ALT levels was observed.,and neither inflammatory cell infiltration nor hepatic necrosis was observed in the liver.(4) As immune response was induced in the lymphocyte in this model, we are trying to isolate T cells from the lymphnode, and inject T cells into portal or systemic vein to investigate the induction of immune response and liver damage. We also made fusions of dendritic cells and ADT. We are trying to make a model for alcoholic hepatitis by chronic ethanol feeding and immunization with this fusion cells.

(1)用以色列等(Proc Nati Acad Sci USA 83：7923,1986)的方法制备小鼠白蛋白-乙醛加合物(ADT)。(2)为了选择对ADT反应良好的小鼠，制备了4种不同品系的小鼠(B10S、BALB/C、C3H和B6小鼠)。用ADT免疫小鼠。每只小鼠的全身淋巴结取淋巴细胞，进行体外淋巴细胞刺激试验。B6小鼠的刺激指数明显高于其他组。(3)将B6小鼠随机分为6组，分别给予免疫和乙醇喂养(10周)。测定了用小鼠白蛋白或ADT培养的淋巴细胞摄取~3H-胸腺嘧啶核苷的刺激指数，ADT免疫的乙醇喂养小鼠的刺激指数显著增加。但血浆AST和ALT水平未见升高，肝脏未见炎性细胞浸润和肝组织坏死。(4)在本模型中，由于在淋巴细胞中诱导了免疫反应，我们试图从淋巴中分离T细胞，并将T细胞注入门静脉或全身静脉，以研究其诱导免疫反应和肝脏损伤的作用。我们还进行了树突状细胞和ADT的融合。我们正试图通过慢性酒精喂养和用这种融合细胞免疫来制作酒精性肝炎的模型。