Buchumschlag

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Pardo, Julián (VerfasserIn) , Bosque, Alberto (VerfasserIn) , Brehm, Reina (VerfasserIn) , Wallich, Reinhard (VerfasserIn) , Naval, Javier (VerfasserIn) , Müllbacher, Arno (VerfasserIn) , Anel, Alberto (VerfasserIn) , Simon, Markus M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2004
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
Volltext
Verfasserangaben:Julián Pardo, Alberto Bosque, Reina Brehm, Reinhard Wallich, Javier Naval, Arno Müllbacher, Alberto Anel, and Markus M. Simon
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 24.02.2021
Beschreibung:Online Resource
ISSN:1540-8140
DOI:10.1083/jcb.200406115

Ähnliche Einträge