| Cathepsin-B-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism of T-cell depletion. | |
| | |
MedLine Citation:
|
PMID: 12893746 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Antithymocyte globulins (ATGs), the immunoglobulin G (IgG) fraction of sera from rabbits or horses immunized with human thymocytes or T-cell lines, are used in conditioning regimens for bone marrow transplantation, in the treatment of acute graft-versus-host disease, in the prevention or treatment of acute rejection in organ transplantation, and in severe bone marrow aplasia. In nonhuman primates, ATGs induce rapid, dose-dependent, T-cell depletion in peripheral lymphoid tissues, where apoptotic cells can be demonstrated in T-cell zones. We show here that increasing ATG concentrations in vitro resulted in reduced lymphocyte proliferative responses, associated with a rapid increase in the percentage of apoptotic cells. Apoptosis did not require prior exposure to interleukin-2, nor did it result in CD178/CD95 or tumor necrosis factor/tumor necrosis factor receptor (TNF/TNF-R) interactions; it was therefore clearly different from activation-induced cell death. Cytochrome c release, caspase-9, and caspase-3 activation were not implicated, excluding a direct involvement of the intrinsic mitochondrial pathway. The cysteine protease inhibitor E64d and cathepsin-B-specific inhibitors conferred significant protection, whereas apoptosis was associated with the release of active cathepsin B into the cytosol. These data demonstrate a role for cathepsin B in T-cell apoptosis induced by ATGs at concentrations achieved during clinical use. |
| | |
Authors:
|
Marie-Cécile Michallet; Frederic Saltel; Xavier Preville; Monique Flacher; Jean-Pierre Revillard; Laurent Genestier |
Related Documents
:
|
9493956 - Cleavage of poly(adp-ribose) polymerase: a sensitive parameter to study cell death. 10502406 - Paclitaxel induces apoptosis in saos-2 cells with cd95l upregulation and bcl-2 phosphor... 14581476 - Selective disruption of lysosomes in hela cells triggers apoptosis mediated by cleavage... 19380466 - Novel subtilase cytotoxin produced by shiga-toxigenic escherichia coli induces apoptosi... 18417356 - Disruption of the gamma c cytokine network in t cells during hiv infection. 20210786 - Inflammatory cell recruitment in cardiovascular disease: murine models and potential cl... |
Publication Detail:
|
Type: Journal Article Date: 2003-07-31 |
Journal Detail:
|
Title: Blood Volume: 102 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2003 Nov |
Date Detail:
|
Created Date: 2003-11-04 Completed Date: 2004-01-05 Revised Date: 2004-11-17 |
Medline Journal Info:
|
Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
|
Languages: eng Pagination: 3719-26 Citation Subset: AIM; IM |
Affiliation:
|
Laboratoire d'Immunopharmacologie, Institut National de la Santé et de la Recherche Médicale U503 and U404, Centre d'Etudes et de Recherche en Virologie et Immunologie, Lyon, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antilymphocyte Serum
/
administration & dosage,
pharmacology* Apoptosis* Caspases Cathepsin B / metabolism, physiology* Cytochromes c Cytosol Dose-Response Relationship, Drug Humans Lymphocyte Activation / drug effects Lymphocyte Depletion / methods* Lysosomes T-Lymphocytes / cytology |
| Chemical | |
Reg. No./Substance:
|
0/Antilymphocyte Serum; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases; EC 3.4.22.1/Cathepsin B |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Quantification of PRV-1 mRNA distinguishes polycythemia vera from secondary erythrocytosis.
Next Document: Identification and characterization of 2 types of erythroid progenitors that express GATA-1 at disti...