Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis

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.

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.

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.

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.