Involvement of natural killer T cells in halothane-induced liver injury in mice.
Involvement of natural killer T cells in halothane-induced liver injury in mice.
复制标题
DOI：
10.1016/j.bcp.2010.03.025
复制
发表时间：
2010-07-15
影响因子：
5.8
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
--
作者：
Cheng, Linling;You, Qiang;Yin, Hao;Holt, Michael P.;Ju, Cynthia
药物性肝损伤（DILI）导致显著的患者发病率和死亡率，并且是停药的最常见原因。必须彻底了解DILI的潜在机制，以有效预测和预防这些反应。我们最近建立了氟烷诱导的肝损伤（HILI）的小鼠模型。本研究的目的是探讨肝自然杀伤T（NKT）细胞在HILI发病机制中的作用。在WT和CD 1d −/−小鼠之间比较HILI的程度，这些小鼠缺乏NKT细胞。数据显示，CD 1d −/−小鼠在发生HILI时具有抗性。这种耐药性似乎是NKT细胞耗竭的直接结果，而不是由于NKT细胞和其他肝脏先天免疫细胞之间不存在串扰而间接导致的。与WT小鼠相比，CD 1d −/−小鼠在氟烷激发后表现出显著较低的肝脏浸润中性粒细胞数量（WT中为470，000 ± 100，000/肝脏，CD 1d −/−小鼠中为120，000 ± 31，500/肝脏）。这一结果与我们先前发现的嗜中性粒细胞在HILI中不可或缺的作用相结合，强烈表明NKT细胞在调节嗜中性粒细胞募集中起关键作用，从而有助于HILI的发展。总的来说，目前的研究和已发表的报告表明，HILI的小鼠模型为研究DILI的潜在机制提供了实验系统。此外，该模型可能会发现易感因素，这些因素可能会控制氟烷和其他潜在药物治疗患者的肝损伤。
Drug-induced liver injury (DILI) causes significant patient morbidity and mortality, and is the most common reason for drug withdrawals. It is imperative to gain a thorough understanding of the underlying mechanisms of DILI to effectively predict and prevent these reactions. We have recently developed a murine model of halothane-induced liver injury (HILI). The aim of the present study was to investigate the role of hepatic natural killer T (NKT) cells in the pathogenesis of HILI. The degrees of HILI were compared between WT and CD1d−/−mice, which are deficient in NKT cells. The data revealed that CD1d−/−mice were resistant in developing HILI. This resistance appeared to be a direct result of NKT cell-depletion rather than an indirect one due to the absence of cross-talk between NKT cells and other hepatic innate immune cells. Compared with WT mice, CD1d−/− mice exhibited a significantly lower number of hepatic infiltrating neutrophils upon halothane challenge (470,000±100,000/liver in WT vs. 120,000±31,500/liver in CD1d−/− mice). This result in conjunction with our previous finding of an indispensable role of neutrophils in HILI strongly suggest that NKT cells play a critical role in regulating neutrophil recruitment, thereby contributing to the development of HILI. Collectively, the current study and published reports indicate that this murine model of HILI provides an experimental system for the investigation of the underlying mechanisms of DILI. In addition, this model may yield the discovery of susceptibility factors that may control the development of liver injury in patients treated with halothane and potentially other drugs.
登录
查看更多内容
影响因子：
13.5
作者：
Cheng, Linling;You, Qiang;Yin, Hao;Holt, Michael;Franklin, Christopher;Ju, Cynthia
通讯作者：
Ju, Cynthia
DOI：
10.1084/jem.179.5.1529
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizuhara H;O'Neill E;Seki N;Ogawa T;Kusunoki C;Otsuka K;Satoh S;Niwa M;Senoh H;Fujiwara H
通讯作者：
Fujiwara H
影响因子：
6.4
作者：
Margalit, M;Shibolet, O;Ilan, Y
通讯作者：
Ilan, Y
影响因子：
29.4
作者：
Liu, ZX;Govindarajan, S;Kaplowitz, N
通讯作者：
Kaplowitz, N
影响因子：
6
作者：
Schümann, J;Wolf, D;Tiegs, G
通讯作者：
Tiegs, G