Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury
Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury
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DOI：
10.1111/j.1478-3231.2005.01216.x
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发表时间：
2006-04-01
影响因子：
6.7
通讯作者：
Mori, M
中科院分区：
文献类型：
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作者：
Nakajima, H;Takagi, H;Mori, M
背景：巨噬细胞移动抑制因子（macrophagemigrationinhibitoryfactor，MIF）是一种重要的免疫调节因子，参与了机体免疫功能的调节. MIF在炎症和免疫介导的疾病中起重要作用，但MIF在肝损伤中的作用尚未阐明。研究方法：本研究采用MIF基因敲除（KO）和野生型（WT）小鼠，从生物化学、组织学和免疫学角度研究了MIF在刀豆球蛋白A（ConA）诱导的T细胞介导的肝损伤中的作用。结果如下：与WT小鼠相比，MIF KO小鼠的血清丙氨酸氨基转移酶值显著降低，肝实质细胞大量坏死和炎性细胞浸润的组织学变化受到抑制。这种保护作用不是由肿瘤坏死因子-α或干扰素-γ介导的，而肿瘤坏死因子-α或干扰素-γ是Con A诱导的肝损伤的关键介质，因为它们的血清浓度在MIF KO和WT小鼠中显示相似。另一方面，流式细胞术分析表明，活化的肝白细胞数量在MIF KO小鼠中比在WT小鼠中减少更多。结论：MIF缺乏对ConA诱导的小鼠肝损伤具有保护作用。控制MIF活性可能是治疗自身免疫性肝炎和病毒性肝炎等T细胞活化相关肝病的有用治疗策略。
Background: Macrophage migration inhibitory factor (MIF) is involved in in. ammatory and immune-mediated diseases but the role of MIF in liver injury has not yet been elucidated. Methods: We investigated biochemically, histologically and immunologically the character of MIF in concanavalin A (Con A)-induced T-cell-mediated liver injury using MIF knockout (KO) mice and wild-type (WT) mice. Results: MIF KO mice showed significantly decreased serum alanine aminotransferase values and suppressed histological change with massive necrosis of the hepatic parenchymal cells and infiltration of inflammatory cells compared with their WT counterparts. This protection was not mediated by either tumor necrosis factor-alpha or interferon-gamma, which are critical mediators of Con A-induced liver injury, as their serum concentrations were shown to be similar in MIF KO and WT mice. On the other hand, a flow cytometric analysis demonstrated that the number of activated hepatic leukocytes decreased more in the MIF KO mice than in the WT mice. Conclusions: A lack of MIF protected the mice from Con A-induced liver injury. Controlling the MIF activity may be a useful therapeutic strategy for treating such T-cell activation-associated liver diseases as autoimmune hepatitis and viral hepatitis.