Immunoregulatory Effects of Phospholipase A₂ (PLA₂) on the Proliferation of Human Lymphocytes

Abstract

Extracellular phospholipase A₂ (PLA₂) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA₂ exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA₂ enhanced the proliferation of PHA MNC (maximal increase was 37.0 ± 5.67%). Conversely, at concentrations over 10 U/ml, PLA₂ markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 ± 2.89%). PLA₂ was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA₂ at a low concentration. In addition, PLA₂ displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA₂, was parallel to the change of percentage of hlper T cells. Furthermore - a CD4-rich population was proved more susceptible to PLA₂ effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA₂, abrogated the biphasic effect of PLA₂ on PHA MNC proliferation. These results suggest that PLA₂ plays a regulatory role on immune reactions by modulating the percentage of helper T cells.

Key Words:

• phospholipase A₂
• helper T cell
• membrane polarization
• immunoregulation
• para-bromophenacyl bromide