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Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process

A M Friedlander

    The Journal of Biological Chemistry
    |June 5, 1986
    PubMed

    Insights

    Anthrax lethal toxin kills macrophages in vitro. The toxin requires acidic endocytic vesicles to enter cells and exert its lethal effect, offering insights into anthrax pathogenesis.

    Area of Science:

    • Toxicology
    • Cell Biology
    • Microbiology

    Background:

    • Anthrax lethal toxin, composed of protective antigen and lethal factor, is lethal to animals.
    • Existing research lacks a defined in vitro system to study toxin lethality.

    Purpose of the Study:

    • To establish the first in vitro system demonstrating the lethality of anthrax lethal toxin.
    • To investigate the cellular mechanisms underlying anthrax lethal toxin-induced cell death.

    Main Methods:

    • Utilized mouse peritoneal macrophages as an in vitro model.
    • Exposed macrophages to varying concentrations of anthrax lethal toxin components.
    • Investigated the role of intracellular pH and endocytosis using chemical agents like amines and monensin.

    Main Results:

    • Mouse peritoneal macrophages were killed within 1 hour of exposure to anthrax lethal toxin.
    • Neither protective antigen nor lethal factor alone exhibited toxicity.
    • Cell protection was achieved by agents that dissipate proton gradients, suggesting a role for acidic vesicles.
    • Protection was reversible and could be overcome by lowering intravesicular pH.

    Conclusions:

    • Anthrax lethal toxin requires entry through acidic endocytic vesicles to induce cytotoxicity.
    • This study provides a novel in vitro model for anthrax toxin research.
    • Findings elucidate a critical step in the mechanism of anthrax toxin action.

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