Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis
Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune CD8(+) T cells from mice deficient in per...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2004
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| In: |
The journal of cell biology
Year: 2004, Jahrgang: 167, Heft: 3, Pages: 457-468 |
| ISSN: | 1540-8140 |
| DOI: | 10.1083/jcb.200406115 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1083/jcb.200406115 Verlag, lizenzpflichtig, Volltext: https://rupress.org/jcb/article/167/3/457/51394 
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| Verfasserangaben: | Julián Pardo, Alberto Bosque, Reina Brehm, Reinhard Wallich, Javier Naval, Arno Müllbacher, Alberto Anel, and Markus M. Simon |
MARC
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| 245 | 1 | 0 | |a Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis |c Julián Pardo, Alberto Bosque, Reina Brehm, Reinhard Wallich, Javier Naval, Arno Müllbacher, Alberto Anel, and Markus M. Simon |
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| 520 | |a Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune CD8(+) T cells from mice deficient in perf, gzmA and/or gzmB, and the Fas-resistant EL4.F15 tumor target cell, we show that (a) CTL from gzmA(-/-) or gzmB(-/-) mice similarly induced early proapoptotic features, such as phosphatidyl serine (PS) exposure on plasma membrane, Delta Psi(m) loss, and reactive oxygen radical generation, though with distinct kinetics; (b) CTL from gzmA(-/-) but not from gzmB(-/-) mice activate caspase 3 and 9; (c) PS exposure induced by CTL from gzmA(-/-) or gzmB(-/-) mice is prevented, respectively, by caspase inhibitors or by reactive oxygen scavengers without interfering with target cell death; and (d) all gzm-induced apoptotic features analyzed depend critically on perf. Thus, perf is the principal regulator in CTL-mediated and gzm-facilitated intracellular processes. The ability of gzmA and gzmB to induce multiple independent cell death pathways may be the hosts response to circumvent evasion strategies of pathogens and tumors. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Cell Line, Tumor | |
| 650 | 4 | |a Cells, Cultured | |
| 650 | 4 | |a Cytotoxicity, Immunologic | |
| 650 | 4 | |a Granzymes | |
| 650 | 4 | |a Kinetics | |
| 650 | 4 | |a Membrane Glycoproteins | |
| 650 | 4 | |a Membrane Potentials | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Mice, Knockout | |
| 650 | 4 | |a Perforin | |
| 650 | 4 | |a Phosphatidylserines | |
| 650 | 4 | |a Pore Forming Cytotoxic Proteins | |
| 650 | 4 | |a Reactive Oxygen Species | |
| 650 | 4 | |a Serine Endopeptidases | |
| 650 | 4 | |a T-Lymphocytes, Cytotoxic | |
| 650 | 4 | |a Time Factors | |
| 700 | 1 | |a Bosque, Alberto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brehm, Reina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wallich, Reinhard |e VerfasserIn |0 (DE-588)1059566710 |0 (DE-627)798640839 |0 (DE-576)163467781 |4 aut | |
| 700 | 1 | |a Naval, Javier |e VerfasserIn |4 aut | |
| 700 | 1 | |a Müllbacher, Arno |e VerfasserIn |4 aut | |
| 700 | 1 | |a Anel, Alberto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Simon, Markus M. |e VerfasserIn |4 aut | |
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