Granzyme B-induced cell death exerted by ex vivo CTL: discriminating requirements for cell death and some of its signs
Date
2008
Authors
Pardo, Julian
Wallich, R
Martin, P
Urban, C
Rongvaux, A
Flavell, R.A.
Mullbacher, Arno
Borner, C
Simon, Markus M
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Stockton Press
Abstract
Granzyme B (gzmB) of cytotoxic T lymphocytes (CTL) is essential for recovery from intracellular pathogens, but the molecular basis of its action is still unresolved. Here, we analyzed gzmB-mediated death pathways under physiological conditions using ex vivo virus-immune CTLs that express perf and gzmB, but not gzmA (gzmB+CTL). We show that gzmB+CTL abrogate target cell proliferation most likely by inducing cell death, independent of caspases and mitochondrial signaling. In addition, the data reveal that gzmB+CTL independently induce pro-apoptotic processes either via caspase-3/-7, leading to plasma membrane perturbance and ROS production or via Bid/Bak/Bax, resulting in cytochrome c release and that both pathways elicit loss of ΔΨm. Our data provide evidence for a pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors.
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Keywords: caspase 3; caspase 7; caspase 9; cytochrome c; granzyme A; granzyme B; perforin; protein Bak; protein Bax; protein Bid; reactive oxygen metabolite; animal cell; apoptosis; article; cell killing; cell membrane permeability; cell membrane potential; cell pr
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Cell Death and Differentiation
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Journal article
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2037-12-31
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