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J. Biol. Chem., Vol. 261, Issue 16, 7123-7126, Jun, 1986
AM Friedlander
Anthrax lethal toxin, which consists of two proteins, protective antigen
and lethal factor, is lethal for experimental animals. This study describes
the first in vitro system demonstrating lethality of the toxin. Mouse
peritoneal macrophages are killed within 1 h of exposure to the toxin.
Neither protein component alone shows any toxic activity. The minimal
effective concentration of protective antigen and lethal factor was
approximately equal to 10(-2) and approximately equal to 10(-3)
micrograms/ml, respectively. None of the several established cell lines
examined was killed. Cells could be completely protected from the toxin by
pretreatment with agents, such as amines or monensin, which dissipate
intracellular proton gradients and raise the pH of intracellular vesicles.
This protection was reversible and could be overcome by lowering the
intravesicular pH. Antitoxin added after preincubation with amines was
unable to protect cells subsequently exposed to low pH treatment. These
results suggest that anthrax lethal toxin requires passage through an
acidic endocytic vesicle in order to exert its toxic effect within the
cytosol.
Macrophages are sensitive to anthrax lethal toxin through an acid- dependent process
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