A soluble receptor decoy protects rats against anthrax lethal toxin challenge

A soluble receptor decoy protects rats against anthrax lethal toxin challenge
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DOI:
10.1086/432731
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发表时间:
2005-09-15
影响因子:
6.4
通讯作者:
Manchester, M
Manchester, M
中科院分区:
医学2区
文献类型:
--
作者:
Scobie, HM;Thomas, D;Manchester, M

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吸入性炭疽的成功暴露后治疗被认为包括中和炭疽毒素。可溶性炭疽毒素受体/肿瘤内皮标记8和毛细血管形态发生蛋白2(sATR/TEM8和sCMG2)受体诱饵分别与炭疽毒素保护性抗原结合,并与细胞受体竞争结合。在这里,我们表明,在中毒的组织培养模型中,sCMG2是一种比SATT/TEM8强11.4倍的抗毒素,这种增强的活性对应于类似于高1000倍的PA结合亲和力。化学计量浓度的sCMG2保护老鼠免受致命毒素的攻击,使sCMG2成为迄今描述的最有效的炭疽抗毒素之一。
Successful postexposure treatment for inhalation anthrax is thought to include neutralization of anthrax toxin. The soluble anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (sATR/TEM8 and sCMG2, respectively) receptor decoys bind to anthrax toxin protective antigen (PA) and compete with cellular receptors for binding. Here, we show that, in a tissue-culture model of intoxication, sCMG2 is a 11.4-fold more potent antitoxin than sATR/TEM8 and that this increased activity corresponds to an similar to 1000- fold higher PA-binding affinity. Stoichiometric concentrations of sCMG2 protect rats against lethal toxin challenge, making sCMG2 one of the most effective anthrax antitoxins described to date.