Logo image
Back
Caspase Dependence of Target Cell Damage Induced by Cytotoxic Lymphocytes
Journal article   Open access   Peer reviewed

Caspase Dependence of Target Cell Damage Induced by Cytotoxic Lymphocytes

Apurva Sarin, Elias K. Haddad and Pierre A. Henkart
The Journal of immunology (1950), v 161(6), pp 2810-2816
15 Sep 1998
DOI: https://doi.org/10.4049/jimmunol.161.6.2810
PMID: 9743340
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://journals.aai.org/jimmunol/article-pdf/161/6/2810/1089435/im189802810o.pdfView
Published, Version of Record (VoR) Open

Abstract

Abstract Since the CTL secreted granule protease granzyme B can activate multiple target caspases, it has been proposed that this pathway is responsible for CTL-induced cytolysis of Fas-negative targets. However, target lysis via the granule exocytosis pathway is completely resistant to caspase inhibitors. To test the possibility that granzymes trigger a postcaspase cytoplasmic apoptotic pathway leading to lysis, we have examined the caspase dependence of several cytoplasmic changes associated with apoptotic death. Rapid prelytic phosphatidylserine externalization was induced in Jurkat target cells by both the Fas ligand (FasL)/Fas and the granule exocytosis effector pathways. This was specifically blocked by peptide ketone caspase inhibitors when induced by the former, but not by the latter, pathway. A rapid prelytic loss of target mitochondrial ψ was also induced by both CTL effector pathways, and this was also specifically blocked by caspase inhibitors when induced by the FasL/Fas, but not by the granule exocytosis, pathway. Similarly, target membrane blebbing induced by CTL via the FasL/Fas, but not via the granule exocytosis, effector pathway was specifically blocked by caspase inhibitors. In contrast to the above nonnuclear damage, CTL-induced target staining by the lipid probe FM1–43 reflecting plasma membrane endocytosis was blocked by caspase inhibitors. Thus, when caspase activation is blocked, the granule exocytosis pathway triggers several parameters of target apoptotic damage in addition to lysis, suggesting that granzymes directly trigger a postcaspase cytoplasmic apoptotic death pathway.

Metrics

7 Record Views
80 citations in Web of Science
83 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Immunology
Logo image