ON THE ROLE OF MACROPHAGES IN ANTHRAX
ON THE ROLE OF MACROPHAGES IN ANTHRAX
复制标题
DOI：
10.1073/pnas.90.21.10198
复制
发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
COLLIER, RJ
中科院分区：
文献类型：
--
作者：
HANNA, PC;ACOSTA, D;COLLIER, RJ
炭疽杆菌是炭疽病的病原体，主要通过其致命毒素的作用，在易感动物中产生全身性休克和死亡。这种毒素在高浓度下诱导体外巨噬细胞溶解，但对其他细胞几乎没有影响。我们发现，当小鼠通过二氧化硅注射专门耗尽巨噬细胞时，它们对毒素产生了抵抗力。通过共注射毒素敏感的培养的巨噬细胞（RAW 264.7细胞）可以恢复敏感性，但通过共注射其他测试的细胞系不能恢复敏感性。这些结果表明，巨噬细胞介导的致命毒素在体内的行动，并引导我们调查它们在哺乳动物宿主的死亡中的作用。亚溶浓度的致死毒素，数量级低于那些需要诱导RAW 264.7细胞裂解，诱导这些细胞表达白细胞介素1（IL-1）和肿瘤坏死因子在体外。针对IL-1的被动免疫或注射IL-1受体拮抗剂保护小鼠免受毒素攻击，而抗肿瘤坏死因子提供的保护很少（如果有的话）。这些结果表明，炭疽引起的全身性休克和死亡主要是由于高水平的细胞因子，主要是IL-1，由巨噬细胞，已被刺激的炭疽致死毒素的影响。
Bacillus anthracis, the causative agent of anthrax, produces systemic shock and death in susceptible animals, primarily through the action of its lethal toxin. This toxin, at high concentrations, induces lysis of macrophages in vitro but shows little or no effect on other cells. We found that when mice were specifically depleted of macrophages by silica injections, they became resistant to the toxin. Sensitivity could be restored by coinjection of toxin-sensitive cultured macrophages (RAW 264.7 cells) but not by coinjection of other cell lines tested. These results implied that macrophages mediate the action of lethal toxin in vivo and led us to investigate their role in death of the mammalian host. Sublytic concentrations of lethal toxin, orders of magnitude lower than those required to induce lysis of RAW 264.7 cells, were found to induce these cells to express interleukin 1 (IL-1) and tumor necrosis factor in vitro. Passive immunization against IL-1 or injection of an IL-1 receptor antagonist protected mice from toxin challenge, whereas anti-tumor necrosis factor provided little, if any, protection. These results imply that systemic shock and death from anthrax result primarily from the effects of high levels of cytokines, principally IL-1, produced by macrophages that have been stimulated by the anthrax lethal toxin.