Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin
Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin
复制标题
DOI：
10.1038/nm1674
复制
发表时间：
2008-01-01
期刊：
影响因子：
82.9
通讯作者：
Qin, Xuebin
中科院分区：
文献类型：
--
作者：
Hu, Weiguo;Ferris, Sean P.;Qin, Xuebin
条件靶向细胞消融是研究人类疾病发病机制和体内细胞功能的有力方法。中间溶素（Intermedilysin， ILY）是一种由中间链球菌分泌的细胞溶解性重组毒素，由于其对人CD59的受体特异性，只能裂解人细胞。我们培育了两种在红细胞（菌株ThCD59(RBC)）和内皮细胞（菌株ThCD59(END)）上表达人CD59的转基因小鼠品系。在ThCD59（RBC）小鼠中静脉注射ILY诱导急性血管内溶血，导致一氧化氮生物利用度降低，血小板活化增加和快速死亡。在ThCD59（END）小鼠中，ILY诱导内皮细胞快速损伤，导致急性死亡和弥散性血管内凝血。此外，我们发现人类血清中含有在任何其他动物物种中未发现的特异性中和抗体。总之，这些结果表明，这种新的快速条件靶向伊利介导的细胞消融技术可以与任何可用的转基因表达系统结合使用，以研究特定细胞群体的生理作用。
Conditional targeted cell ablation is a powerful approach for investigating the pathogenesis of human diseases and in vivo cellular functions. Intermedilysin (ILY) is a cytolytic poreforming toxin secreted by Streptococcus intermedius that lyses human cells exclusively, owing to its receptor specificity for human CD59. We generated two transgenic mouse strains that express human CD59 either on erythrocytes (strain ThCD59(RBC)) or on endothelia (strain ThCD59(END)). Intravenous injection of ILY in ThCD59(RBC) mice induced acute intravascular hemolysis, leading to reduced nitric oxide bioavailability, increased platelet activation and rapid death. In ThCD59(END) mice, ILY induced rapid endothelial damage, leading to acute death and disseminated intravascular coagulation. Additionally, we show that human serum contains ILY-specific neutralizing antibodies not found in any other animal species. Together, these results suggest that this new rapid conditional targeted ILY-mediated cell ablation technique can be used in combination with any available transgenic expression system to study the physiologic role of specific cell populations.