Development and characterization of a rodent model of immune-mediated cholangitis.
Development and characterization of a rodent model of immune-mediated cholangitis.
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免疫介导的胆管炎啮齿动物模型的开发和表征。
DOI：
10.1073/pnas.93.1.216
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发表时间：
1996
影响因子：
11.1
通讯作者：
LaRusso,NF
中科院分区：
文献类型：
--
作者：
Ueno,Y;Phillips,JO;Ludwig,J;Lichtman,SN;LaRusso,NF
胆管病是一组肝胆疾病，其中肝内胆管上皮细胞或胆管细胞是各种破坏性过程的靶点，包括免疫介导的损伤。我们测试了这一假设，胆管炎可以诱导啮齿动物免疫与高度纯化的胆管细胞。用纯化的增生胆管细胞从同系Wistar大鼠或同种异体Fischer 344大鼠胆管结扎后分离免疫近交系Wistar大鼠;用牛血清白蛋白（BSA）或肝细胞免疫对照大鼠。用胆管细胞免疫后，受体动物出现了非化脓性胆管炎的组织学证据，而其他器官没有炎症;用BSA或肝细胞免疫的组没有显示胆管炎。免疫组化研究显示，胆管周围的门静脉浸润由CD 3阳性淋巴细胞组成，其中一些表达主要组织相容性复合物II类抗原; B细胞和外源性单核细胞/巨噬细胞基本上不存在。将未分级ConA刺激的脾细胞从胆管细胞免疫（但不是BSA免疫）大鼠转移到受体中也引起非化脓性胆管炎。此外，这些脾细胞从胆管细胞免疫（但不是BSA免疫）大鼠在体外培养的啮齿类动物胆管细胞的细胞毒性，没有观察到对大鼠肝细胞系的细胞毒性。此外，对胆管细胞蛋白质的免疫印迹证明了特异性抗体反应的血清中的胆管细胞免疫的大鼠。最后，胆管细胞免疫大鼠的胆管造影显示整个肝内胆管系统的扭曲和迂曲。这种独特的实验性胆管炎啮齿动物模型证明了免疫机制在胆管炎发病机制中的重要性，并将证明有助于探索免疫系统靶向和损伤胆管细胞的机制。
The cholangiopathies are a group of hepatobiliary diseases in which intrahepatic bile duct epithelial cells, or cholangiocytes, are the target for a variety of destructive processes, including immune-mediated damage. We tested the hypothesis that cholangitis could be induced in rodents by immunization with highly purified cholangiocytes. Inbred Wistar rats were immunized with purified hyperplastic cholangiocytes isolated after bile duct ligation from either syngeneic Wistar or allogeneic Fischer 344 rats; control rats were immunized with bovine serum albumin (BSA) or hepatocytes. After immunization with cholangiocytes, recipient animals developed histologic evidence of nonsuppurative cholangitis without inflammation in other organs; groups immunized with BSA or hepatocytes showed no cholangitis. Immunohistochemical studies revealed that portal tract infiltrates around bile ducts consisted of CD3-positive lymphocytes, some of which expressed major histocompatibility complex class II antigen; B cells and exogenous monocytes/macrophages were essentially absent. Transfer of unfractionated ConA-stimulated spleen cells from cholangiocyte-immunized (but not BSA-immunized) rats into recipients also caused nonsuppurative cholangitis. Moreover, these splenocytes from cholangiocyte-immunized (but not BSA-immunized) rats were cytotoxic in vitro for cultured rodent cholangiocytes; no cytotoxicity was observed against a rat hepatocyte cell line. Also, a specific antibody response in sera of cholangiocyte-immunized rats was demonstrated by immunoblots against cholangiocyte proteins. Finally, cholangiograms in cholangiocyte-immunized rats showed distortion and tortuosity of the entire intrahepatic biliary ductal system. This unique rodent model of experimental cholangitis demonstrates the importance of immune mechanisms in the pathogenesis of cholangitis and will prove useful in exploring the mechanisms by which the immune system targets and damages cholangiocytes.