A T-CELL-DEPENDENT EXPERIMENTAL LIVER-INJURY IN MICE INDUCIBLE BY CONCANAVALIN-A
A T-CELL-DEPENDENT EXPERIMENTAL LIVER-INJURY IN MICE INDUCIBLE BY CONCANAVALIN-A
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DOI：
10.1172/jci115836
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发表时间：
1992-07-01
影响因子：
15.9
通讯作者：
WENDEL, A
中科院分区：
文献类型：
--
作者：
TIEGS, G;HENTSCHEL, J;WENDEL, A
当静脉内给予> 1.5 mg/kg伴刀豆球蛋白A（Con A）时，雄性NMRI或BALB/c小鼠在8 h内出现严重肝损伤，通过转氨酶释放进行评估。组织学上，只有肝脏受到影响。电镜下可见白细胞粘附于内皮细胞，肝细胞形成水泡。凝集素的肝毒性既不与其凝集活性，也不与其糖特异性。给予0.5 mg/kg地塞米松或50 mg/kg环孢素A或50 mg/kg FK 506（Fujimycin）可保护动物，而吲哚美辛预处理未能保护动物。Con A肝炎伴随着IL-2释放到动物血清中。缺乏B和T淋巴细胞的严重联合免疫缺陷综合征小鼠对Con A具有抵抗性。具有未成熟T淋巴细胞的无胸腺裸鼠也是耐药的。用抗T淋巴细胞的抗体预处理小鼠完全保护免受Con A的侵害，单克隆抗小鼠CD 4也是如此。单克隆抗小鼠CD 8未能保护。用二氧化硅颗粒预处理小鼠，即，删除巨噬细胞，防止肝炎的诱导。这些发现提供了证据，表明Con A诱导的肝损伤依赖于巨噬细胞在Con A存在下激活T淋巴细胞。该模型可能允许免疫介导的肝脏疾病，如自身免疫性慢性活动性肝炎的病理生理学的研究。
Male NMRI or BALB/c mice developed severe liver injury as assessed by transaminase release within 8 h when an intravenous dose > 1.5 mg/kg concanavalin A (Con A) was given. Histopathologically, only the liver was affected. Electron micrographs revealed leukocyte sticking to endothelial cells and bleb formation of hepatocytes. The hepatotoxicity of the lectin correlated neither with its agglutination activity nor with its sugar specificity. Administration of 0.5 mg/kg dexamethasone or 50 mg/kg cyclosporine A or 50 mg/kg FK 506 (Fujimycin) resulted in protection of the animals whereas indomethacin pretreatment failed to protect. Con A hepatitis was accompanied by the release of IL-2 into the serum of the animals. Mice with severe combined immunodeficiency syndrome lacking B as well as T lymphocytes were resistant against Con A. Athymic nude mice with immature T lymphocytes were also resistant. Pretreatment of mice with an antibody against T lymphocytes fully protected against Con A as did monoclonal anti-mouse CD4. Monoclonal anti-mouse CD8 failed to protect. Pretreatment of mice with silica particles, i.e., deletion of macrophages, prevented the induction of hepatitis. These findings provide evidence that Con A-induced liver injury depends on the activation of T lymphocytes by macrophages in the presence of Con A. The model might allow the study of the pathophysiology of immunologically mediated hepatic disorders such as autoimmune chronic active hepatitis.