Linked Life Data

16085564

Source:http://linkedlifedata.com/resource/pubmed/id/16085564

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-8-8
pubmed:abstractText
Elimination of tumor cells by cytotoxic T lymphocytes (CTL) is mediated by two major pathways: the granule exocytosis and the death receptor pathway, transduced by Fas, TNF and TRAIL. The usage of these distinct pathways in the alloreactive setting across major and minor HLA barriers still remains controversial. We generated CTLs against allogeneic Epstein-Barr virus (EBV)-transformed cell lines (LCL) from HLA-unmatched healthy donors and assessed their cytotoxicity by flow cytometrically measuring mitochondrial membrane permeability (MMP) of target cells. Mitochondrial apoptosis induced by CTL was abrogated by selectively inhibiting the granule exocytosis-mediated pathway with Concanamycin A (CMA). Conversely, apoptosis was not decreased in the presence of the caspase 8 inhibitor IETD, which is specific for all death receptor pathways. In general, caspases were not involved in MMP as shown using the pan-caspase inhibitor zVAD. This effector mechanism was preserved when using purified CD4 + and CD8 + T-lymphocyte subsets to generate CTL. We further showed, that death receptor signalling was not used as a salvage mechanism when granule exocytosis was inhibited even at longer incubation times sufficient for slow kinetic death receptor caspase signalling. Our results clearly demonstrate that mitochondrial apoptosis induced by human alloreactive CTLs is mainly mediated by granule exocytosis but not by death receptor caspase dependent pathways. Furthermore, the granule exocytosis pathway does not require caspases to induce MMP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1042-8194
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1207-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
The death receptor pathway is not involved in alloreactive T-cell induced mitochondrial membrane permeability.
pubmed:affiliation
Division of Haematology/Oncology, Daprtment of Medicine, Freiburg University Hospital, University of Freiburg, Germany. gruellich@mm11.ukl.uni-freiburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't