A new experimental murine model for lipopolysaccharide-mediated lethal shock with lung injury
A new experimental murine model for lipopolysaccharide-mediated lethal shock with lung injury
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DOI：
10.1177/1753425911410236
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发表时间：
2012-04
期刊：
影响因子：
3.2
通讯作者：
T. Yokochi
中科院分区：
文献类型：
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作者：
T. Yokochi
我们最近建立了一种新的实验小鼠模型，用于脂多糖（LPS）介导的致死性休克和肺特异性损伤。给 α-半乳糖神经酰胺 (α-GalCer) 致敏的小鼠注射脂多糖 (LPS) 会导致严重的肺损伤；小鼠在24小时内因急性肺损伤和呼吸窘迫而死亡。 α-GalCer 激活肺和肝脏中的自然杀伤 T (NKT) 细胞，并诱导干扰素 (IFN)-γ 的产生。然而，IFN-γ 信号传导仅在肺部触发，使肺部容易受到 LPS 的影响。另一方面，IFN-γ信号在肝脏中受到抑制，导致很少的肝脏病变。与肝 NKT 细胞不同，肺 NKT 细胞无法产生白细胞介素 (IL)-4，后者会响应 α-GalCer 下调 IFN-γ 信号传导。肺和肝 NKT 细胞之间不同的细胞因子谱可能导致器官特异性肺部病变。使用 α-GalCer 致敏的实验系统可能是临床内毒素或脓毒性休克的有用实验模型，因为它呈现呼吸衰竭，这是严重脓毒症患者的典型表现。本综述提供了LPS介导的α-GalCer致敏小鼠肺特异性损伤的关键证据和详细机制的介绍。特别是，模型中肺损伤器官特异性发展的分子背景受到关注。
We have recently established a new experimental murine model for lipopolysaccharide (LPS)-mediated lethal shock with lung-specific injury. Severe lung injury is induced by administration of LPS into α-galactosylceramide (α-GalCer)-sensitized mice; the mice died with acute lung injury and respiratory distress within 24 h. α-GalCer activates natural killer T (NKT) cells in the lungs and liver, and induces the production of interferon (IFN)-γ. However, IFN-γ signaling is only triggered in the lungs and makes them susceptible to LPS. On the other hand, IFN-γ signaling is inhibited in liver and results in few hepatic lesions. Unlike liver NKT cells, lung NKT cells fail to produce interleukin (IL)-4, which down-regulates the IFN-γ signaling, in response to α-GalCer. The differential cytokine profile between lung and liver NKT cells may lead to organ-specific lung lesions. The experimental system using α-GalCer sensitization could be a useful experimental model for clinical endotoxic or septic shock as it presents respiratory failure, a typical manifestation in severe septic patients. In this review, key evidence and the introducuction of the detailed mechanism of LPS-mediated lung-specific injury in α-GalCer-sensitized mice is provided. In particular, the molecular background of organ-specific development of lung injury in the model is focused on.