Popov Serguei G, Villasmil Rafael, Bernardi Jessica, Grene Edith, Cardwell Jennifer, Wu Aiguo, Alibek Darya, Bailey Charles, Alibek Ken
Hadron Advanced Biosystems, Inc., 10900 University Boulevard, MSN 1A8, Manassas, VA 20110, USA.
Biochem Biophys Res Commun. 2002 Apr 26;293(1):349-55. doi: 10.1016/S0006-291X(02)00227-9.
Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity.
致死毒素是炭疽的一种主要毒力因子，可导致实验动物迅速死亡。致死毒素能够进入大多数细胞类型，但只有某些巨噬细胞和细胞系对毒素介导的细胞溶解敏感。我们已经证明，在小鼠RAW 264.7细胞中，亚裂解量的致死毒素会引发典型的凋亡细胞内信号事件，包括膜通透性改变、线粒体膜电位丧失和DNA片段化。半胱天冬酶-1、-2、-3、-4、-6和-8的特异性抑制剂可保护细胞免受毒素侵害。亚裂解浓度的致死毒素会抑制巨噬细胞的吞噬活性。用炭疽（斯特恩）芽孢感染细胞会损害其杀菌能力，而致死毒素抑制剂贝司他汀可逆转这种情况。我们认为，凋亡而非直接裂解与致死毒素的细胞内活性在生物学上相关。
