Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis.
OBJECTIVE
Apoptosis is being increasingly regarded as a key component in the development and progression of atherosclerosis. Since it has become apparent that the immune system plays a predominant role in mediating atherogenesis, there has been a growing recognition that the evaluation of lymphocyte apoptosis may contribute to understanding a persistent altered immune and inflammatory response. The aim of the present study was to evaluate the apoptotic effect of lysophosphatidylcholine (LPC) on peripheral blood lymphocytes (PBL) derived from unstable angina (UA) patients, as compared to healthy donors.


METHODS
PBL isolated from 27 healthy donors and 25 age matched UA patients were examined. Early apoptotic events induced by LPC in resting and phytohemagglutinin (PHA)-activated lymphocytes were evaluated by several apoptotic assays. The levels of intracellular reactive oxygen species (ROS) and the expression of apoptotic regulated proteins (Bcl-2 and Bax) were measured.


RESULTS
LPC was found to induce apoptosis in normal activated lymphocytes, in a dose- and time-dependent manner, in association with an increase in intracellular ROS. In UA patients, an exposure of PHA-activated PBL to LPC triggered neither an increase in ROS generation, nor in the apoptotic manifestations, and was associated with a significantly lower ratio of Bax/Bcl-2 expression.


CONCLUSIONS
Our results indicate that PBL isolated from UA patients may be resistant to apoptosis induction by LPC, resulting from oxidative stress challenge and dysregulation of apoptosis-related protein expression.
The Biophysical Interdisciplinary Schottenstein Center for the Research and the Technology of the Cellome, Department of Physics, Bar Ilan University, Ramat Gan, Israel.
Naomi
N
Zurgil
Elena
E
Afrimzon
Yana
Y
Shafran
Ora
O
Shovman
Boris
B
Gilburd
Haim
H
Brikman
Yehuda
Y
Shoenfeld
Mordechai
M
Deutsch
D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D048429:Cell Size / Q000187:drug effects; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013194:Staining and Labeling
D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species