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J. Biol. Chem., Vol. 278, Issue 9, 7413-7421, February 28, 2003
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From the Macrophages from different inbred
mouse strains exhibit striking differences in their sensitivity to
anthrax lethal toxin (LeTx)-induced cytolysis. Although LeTx-induced
cytolysis of macrophages plays an important role in the outcome of
anthrax infection, the sensitivity of macrophages in vitro
does not correlate with in vivo susceptibility to infection
of Bacillus anthracis. This divergence suggests that
additional factors other than LeTx are involved in the cytolysis of
LeTx-resistant macrophages in vivo. We found that
LeTx-resistant macrophages became sensitive to LeTx-induced cytolysis
when these cells were activated by bacterial components. Tumor necrosis
factor-
Sensitizing Anthrax Lethal Toxin-resistant Macrophages
to Lethal Toxin-induced Killing by Tumor Necrosis
Factor-
*
§¶,§,,,
, and**
Department of Immunology, Scripps Research
Institute, La Jolla, California 92037 and the Van Andel
Research Institute, Grand Rapids, Michigan 49503
induced by bacterial components was a key factor that
cooperated with LeTx in inducing LeTx-resistant macrophage death. Tumor
necrosis factor-/LeTx-induced death of LeTx-resistant macrophages
was dependent on mTor (mammalian target of rapamycin), but independent of caspases. Our
data indicate that host responses to anthrax infection contribute to
cytolysis of LeTx- resistant macrophages.
*
This work was supported in part by National Institutes of
Health Grant AI-41637 and a grant from the California Cancer Research Program (to J. H.). This is Publication 15156-IMM from the Department of Immunology, Scripps Research Institute (La Jolla, CA).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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