Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock.
Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock.
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发表时间：
2006
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通讯作者：
Hiroyasu Ito;N. Koide;F. Hassan;S. Islam;G. Tumurkhuu;I. Mori;T. Yoshida;S. Kakumu;H. Moriwaki-H.-Mor
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作者：
Hiroyasu Ito;N. Koide;F. Hassan;S. Islam;G. Tumurkhuu;I. Mori;T. Yoshida;S. Kakumu;H. Moriwaki-H.-Mor
检查了α-半乳糖神经酰胺（α-GalCer）对脂多糖（LPS）介导的致死率的影响。LPS的施用杀死了用α-GalCer预处理的所有小鼠，但未处理的对照小鼠没有。α-GalCer致敏小鼠的致死性休克伴随着严重的肺部病变，伴有明显的炎症细胞浸润和大量细胞死亡。另一方面，肝脏病变为局灶性和轻度。肺和肝病变中的许多细胞发生凋亡性细胞死亡。α-GalCer致敏作用对于在Valpha 14阳性自然杀伤T细胞缺陷型小鼠中发生系统性致死性休克是无效的。用α-GalCer致敏导致高水平干扰素（IFN）-γ的循环，并进一步增强响应于LPS的肿瘤坏死因子（TNF）-α的产生。通过施用抗IFN-γ或TNF-α抗体消除致死性休克。此外，在TNF-α缺陷小鼠中未发生致死性休克。总之，α-GalCer致敏使小鼠对LPS介导的致死性休克非常敏感，并且发现IFN-γ和TNF-α分别在全身致死性休克的准备和执行中起关键作用。使用α-GalCer致敏的LPS介导的致死性休克可能对采用脓毒症和脓毒性休克实验模型的研究人员有用。
The effect of alpha-galactosylceramide (alpha-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with alpha-GalCer, but not untreated control mice. The lethal shock in alpha-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. alpha-GalCer sensitization was ineffective for the development of the systemic lethal shock in Valpha14-positive natural killer T cell-deficient mice. Sensitization with alpha-GalCer led to the circulation of a high level of interferon (IFN)-gamma and further augmented the production of tumor necrosis factor (TNF)-alpha in response to LPS. The lethal shock was abolished by the administration of anti-IFN-gamma or TNF-alpha antibody. Further, the lethal shock did not occur in TNF-alpha-deficient mice. Taken together, alpha-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-gamma and TNF-alpha were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using alpha-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.