Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences
Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences
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DOI：
10.1073/pnas.0500508102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Kaufmann, SHE
中科院分区：
文献类型：
--
作者：
Kim, C;Gajendran, N;Kaufmann, SHE
由炭疽芽孢杆菌引起的炭疽病是一种主要的生物恐怖威胁。炭疽杆菌产生致死毒素(LeTx)，这是一种致死因子(LF)和保护性抗原的组合，在炭疽病的发病中起主要作用。我们证明人中性粒细胞α-防御素是LF的有效抑制物。人中性粒细胞蛋白(HNP-1)对LF的抑制作用是非竞争性的。HNP-1抑制LeTx处理的巨噬细胞中丝裂原活化蛋白激酶的裂解，并恢复受损的丝裂原活化蛋白激酶信号。HNP-1从炭疽杆菌诱导的细胞毒性中拯救了小鼠巨噬细胞，并在体内用HNP-1-3保护小鼠免受LeTx的致命后果。
Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil alpha-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.