Journal article
Mitochondria control of cell death induced by anti-HLA-DR antibodies
Leukemia, Vol.17(7), pp.1357-1365
2003
DOI: 10.1038/sj.leu.2402976
PMID: 12835725
Abstract
We have previously reported that crosslinking HLA-DR directly induces programmed cell death of malignant B cells. The present study further characterizes the biochemical mechanism for HLA-DR-mediated programmed cell death of tumor cells. Phosphatidylserine exposure on the plasma membrane and propidium iodide incorporation occur with very rapid kinetics and are observed as early as 10 min after the induction of cell death with anti-HLA-DR. In striking contrast to anti-CD95, we observe no activation of caspase-3, -8, or -9 upon anti-HLA-DR addition. Furthermore, the irreversible caspase inhibitor Z-VAD.fmk also failed to inhibit anti-HLA-DR-mediated cell death, further supporting the conclusion that HLA-DR induces cell death via a caspase-independent mechanism. We demonstrate that anti-HLA-DR-induced cell death is instead associated with a rapid disruption of the inner mitochondrial transmembrane potential, ΔΨm, a process that is significantly inhibited by Bcl-2 overexpression. Furthermore, we find that ΔΨm disruption results in the selective release of apoptosis-inducing factor (AIF) from the mitochondria. We propose that AIF is acting to initiate the morphological and biochemical changes observed in HLA-DR-mediated cell death.
Details
- Title: Subtitle
- Mitochondria control of cell death induced by anti-HLA-DR antibodies
- Creators
- S. K BAINS - Protein Design Labs, Inc., Department of Oncology, Fremont, CA, United StatesA MONE - Division of Hematology-Oncology, The Ohio State University, Columbus, OH, United StatesJ. Yun Tso - Protein Design Labs, Inc., Department of Oncology, Fremont, CA, United StatesD LUCAS - The Ohio State UniversityJ. C BYRD - Division of Hematology-Oncology, The Ohio State University, Columbus, OH, United StatesG. J WEINER - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United StatesJ. M GREEN - Protein Design Labs, Inc., Department of Oncology, Fremont, CA, United States
- Resource Type
- Journal article
- Publication Details
- Leukemia, Vol.17(7), pp.1357-1365
- DOI
- 10.1038/sj.leu.2402976
- PMID
- 12835725
- NLM abbreviation
- Leukemia
- ISSN
- 0887-6924
- eISSN
- 1476-5551
- Publisher
- Nature Publishing
- Language
- English
- Date published
- 2003
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094401102771
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