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- W1532593552 abstract "Anthrax lethal toxin (LT) is comprised of protective antigen and lethal factor. Lethal factor enters mammalian cells in a protective antigen-dependent process and cleaves mitogen-activated protein kinase kinases. Although LT has no observable effect on many cell types, it causes necrosis in macrophages derived from certain mouse strains and apoptosis in activated mouse macrophages. In this study, we observed that LT treatment of three different human monocytic cell lines U-937, HL-60 and THP-1 did not induce cell death. Cells did become susceptible to the toxin, however, after differentiation into a macrophage-like state. Treatment with LT resulted in decreased phosphorylation of p38, ERK1/2 and JNK in both undifferentiated and differentiated HL-60 cells, suggesting that the change in susceptibility does not result from differences in toxin delivery or substrate cleavage. Death of differentiated HL-60 cells was accompanied by chromosome condensation and DNA fragmentation, but was not inhibited by the pan-caspase inhibitor Z-VAD-FMK. In addition, we observed that the macrophage differentiation process could be inhibited by LT. Our results indicate that LT-mediated death of mouse and human macrophages may occur through distinct processes and that the differentiation state of human cells can determine susceptibility or resistance to LT." @default.
- W1532593552 created "2016-06-24" @default.
- W1532593552 creator A5011174764 @default.
- W1532593552 creator A5063088784 @default.
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- W1532593552 date "2004-12-10" @default.
- W1532593552 modified "2023-10-18" @default.
- W1532593552 title "Differentiation of human monocytic cell lines confers susceptibility to Bacillus anthracis lethal toxin" @default.
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- W1532593552 doi "https://doi.org/10.1111/j.1462-5822.2004.00458.x" @default.
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