Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis
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Pardo, Julian; Bosque, Alberto; Brehm, R; Wallich, Reinhard; Naval, Javier; Mullbacher, Arno; Anel, A; Simon, Markus M
Description
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)...[Show more]
dc.contributor.author | Pardo, Julian | |
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dc.contributor.author | Bosque, Alberto | |
dc.contributor.author | Brehm, R | |
dc.contributor.author | Wallich, Reinhard | |
dc.contributor.author | Naval, Javier | |
dc.contributor.author | Mullbacher, Arno | |
dc.contributor.author | Anel, A | |
dc.contributor.author | Simon, Markus M | |
dc.date.accessioned | 2015-12-13T22:38:13Z | |
dc.date.available | 2015-12-13T22:38:13Z | |
dc.identifier.issn | 0021-9525 | |
dc.identifier.uri | http://hdl.handle.net/1885/77455 | |
dc.description.abstract | 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, ΔΨm loss, and reactive oxygen radical generation, though with distinct kinetics; (b) CTL from gzmA-l- but not from gzmB-l- 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. | |
dc.publisher | Rockefeller University Press | |
dc.source | Journal of Cell Biology | |
dc.subject | Keywords: benzyloxycarbonylaspartylglutamylvalylaspartyl fluoromethyl ketone; benzyloxycarbonylvalylalanylaspartyl fluoromethyl ketone; caspase 3; caspase 9; endonuclease; endonuclease ape 1; granzyme A; granzyme B; perforin; phosphatidylserine; reactive oxygen met | |
dc.title | Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 167 | |
dc.date.issued | 2004 | |
local.identifier.absfor | 110799 - Immunology not elsewhere classified | |
local.identifier.ariespublication | MigratedxPub6316 | |
local.type.status | Published Version | |
local.contributor.affiliation | Pardo, Julian, Max Planck Institute of Immunobiology | |
local.contributor.affiliation | Bosque, Alberto, Universidad de Zaragoza | |
local.contributor.affiliation | Brehm, R, Max Planck Institute of Immunobiology | |
local.contributor.affiliation | Wallich, Reinhard, Max Planck Institute of Immunobiology | |
local.contributor.affiliation | Naval, Javier, Universidad de Zaragoza | |
local.contributor.affiliation | Mullbacher, Arno, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Anel, A, Universidad de Zaragoza | |
local.contributor.affiliation | Simon, Markus M, Max Planck Institute of Immunobiology | |
local.bibliographicCitation.issue | 3 | |
local.bibliographicCitation.startpage | 457 | |
local.bibliographicCitation.lastpage | 468 | |
local.identifier.doi | 10.1083/jcb.200406115 | |
dc.date.updated | 2016-02-24T09:48:48Z | |
local.identifier.scopusID | 2-s2.0-8444249247 | |
Collections | ANU Research Publications |
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