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首页> 外文期刊>Infection and immunity >Characterization of macrophage sensitivity and resistance to anthrax lethal toxin.
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Characterization of macrophage sensitivity and resistance to anthrax lethal toxin.

机译：表征巨噬细胞对炭疽致死毒素的敏感性和抗性。

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Anthrax lethal toxin, which consists of two proteins, protective antigen and lethal factor, is cytolytic for macrophages. Macrophages from different mouse strains were found to vary in their sensitivities to toxin. C3H mouse macrophages lysed by lethal factor concentrations of 0.001 micrograms/ml were 100,000 times more sensitive than those from resistant A/J mice. We analyzed various stages of the intoxication process to determine the basis for this resistance. Direct binding studies with radioiodinated protective antigen revealed that the affinity (Kd, approximately 0.5 nM) and number of receptors per cell (25,000 to 33,000) were the same in sensitive and resistant cells. Proteolytic activation of protective antigen by a cell surface protease and subsequent binding of lethal factor were also the same in both sensitive and resistant macrophages. Resistant A/J macrophages were not cross-resistant to other toxins and a virus which, like lethal toxin, require vesicular acidification for activity, implying that resistance is not due to a defect in vesicular acidification. When introduced into the cytosol by osmotic lysis of pinosomes, lethal factor in the absence of protective antigen was cytolytic for the sensitive macrophages while resistant cells were unaffected. Thus, lethal factor by itself possesses the toxic activity of lethal toxin. These results suggest that macrophage resistance is due to a defect at a stage occurring after toxin internalization. A/J macrophages may lack the putative lethal factor target in the cytosol or be defective in the further processing or activation of lethal factor in the cytosol or in endocytic vesicles.
机译：炭疽致死毒素由巨噬细胞裂解，该毒素由保护性抗原和致死因子两种蛋白质组成。发现来自不同小鼠品系的巨噬细胞对毒素的敏感性不同。被致死因子浓度为0.001微克/毫升裂解的C3H小鼠巨噬细胞的敏感性比抗A / J小鼠的巨噬细胞高100,000倍。我们分析了醉酒过程的各个阶段，以确定这种抗药性的基础。用放射性碘标记的保护性抗原进行的直接结合研究表明，在敏感性和耐药性细胞中，亲和力（Kd，约0.5 nM）和每个细胞的受体数量（25,000至33,000）相同。在敏感和耐药巨噬细胞中，细胞表面蛋白酶对保护性抗原的蛋白水解激活以及随后的致死因子结合也相同。抗性A / J巨噬细胞对其他毒素和像致命毒素一样需要水泡酸化才能发挥活性的病毒没有交叉抗性，这表明抗药性不是由于水泡酸化的缺陷引起的。当通过脂质体的渗透裂解将其引入细胞质中时，在没有保护性抗原的情况下，致死因子对敏感的巨噬细胞具有细胞溶解作用，而抗性细胞则不受影响。因此，致死因子本身具有致命毒素的毒性。这些结果表明，巨噬细胞抗性归因于毒素内在化后发生的阶段的缺陷。 A / J巨噬细胞可能在细胞质中缺乏假定的致死因子靶标，或者在细胞质或内吞囊泡中的致死因子的进一步加工或激活方面存在缺陷。

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