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Caspase-Independent Phosphatidylserine Exposure During Apoptosis of Primary T Lymphocytes
- Source :
- The Journal of Immunology. 169:4805-4810
- Publication Year :
- 2002
- Publisher :
- The American Association of Immunologists, 2002.
-
Abstract
- Exposure of phosphatidylserine (PS) on the outer leaflet of the plasma membrane is a key feature of apoptosis. As the signals underlying these phenomena are unknown, it is generally assumed that PS exposure is a consequence of caspase activation, another hallmark of apoptosis. In this study we investigated the role of caspases in PS externalization during apoptosis of activated PBL triggered by drugs (etoposide, staurosporine), CD95 engagement, or IL-2 withdrawal. Anti-CD95 mAb induces a rapid activation of caspases, followed by PS exposure and mitochondrial transmembrane potential (ΔΨm) disruption. In contrast, etoposide (ETO), staurosporine (STS), or IL-2 withdrawal triggers concomitant caspase activation, PS exposure, and ΔΨm disruption. Such kinetics suggest that PS exposure could be independent of caspase activation. As expected, in activated PBL treated by anti-CD95 mAb, the pan-caspase inhibitor Cbz-Val-Ala-Asp(OMe)-fluoromethylketone and the caspase-8 inhibitor Cbz-Leu-Glu-Thr-Asp(OMe)-fluoromethylketone, but not the caspase-9 inhibitor Cbz-Leu-Glu-His-Asp(OMe)-fluoromethylketone, inhibit PS externalization and ΔΨm disruption. Surprisingly, during apoptosis induced by ETO, STS, or IL-2 withdrawal, none of those caspase inhibitors prevents PS externalization or ΔΨm disruption, whereas they all inhibit DNA fragmentation as well as the morphological features of nuclear apoptosis. In Jurkat and H9 T cell lines, as opposed to activated PBL, PS exposure is inhibited by Cbz-Val-Ala-Asp(OMe)-fluoromethylketone during apoptosis induced by CD95 engagement, ETO, or STS. Thus, caspase-independent PS exposure occurs in primary T cells during apoptosis induced by stimuli that do not trigger death receptors.
- Subjects :
- Immunology
Apoptosis
Caspase 3
DNA Fragmentation
Phosphatidylserines
Caspase 8
Permeability
Amino Acid Chloromethyl Ketones
Membrane Potentials
Jurkat Cells
chemistry.chemical_compound
T-Lymphocyte Subsets
Tumor Cells, Cultured
medicine
Humans
Immunology and Allergy
Staurosporine
Cells, Cultured
Caspase
Etoposide
Cell Nucleus
Caspase-9
biology
Intracellular Membranes
Phosphatidylserine
Caspase Inhibitors
Caspase 9
Mitochondria
Cell biology
Enzyme Activation
Kinetics
chemistry
Biochemistry
Caspases
biology.protein
Interleukin-2
DNA fragmentation
medicine.drug
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....65ada85738242ef17c032f93dfd829af
- Full Text :
- https://doi.org/10.4049/jimmunol.169.9.4805