Interaction of low molecular weight group IIA phospholipase A2 with apoptotic human T cells:: role of heparan sulfate proteoglycans

Human group IIA phospholipase A(2) (hIIA PLA(2)) is a 14 kDa secreted enzyme associated with inflammatory diseases. A newly discovered property of hIIA PLA(2) is the binding affinity for the heparan sulfate proteoglycan (HSPG) glypican-1. In this study, the binding of hIIA PLA(2) to apoptotic human T cells was investigated. Little or no exogenous hIIA PLA(2) bound to CD3-activated T cells but significant binding was measured on activated T cells induced to undergo apoptosis by anti-CD95. Binding to early apoptotic T cells was greater than to late apoptotic cells. The addition of heparin and the hydrolysis of HSPG by heparinase III only partially inhibited hIIA PLA(2) binding to apoptotic cells, suggesting an interaction with both HSPG and other binding protein(s). Two low molecular weight HSPG were coimmunoprecipitated with hIIA PLA(2) from apoptotic T cells, but not from living cells. Treatment of CD95-stimulated T cells with hIIA PLA(2) resulted in the release of arachidonic acid but not oleic acid from cells and this release was blocked by heparin and heparinase III. Altogether, these results suggest a role for hIIA PLA(2) in the release of arachidonic acid from apoptotic cells through interactions with HSPG and its potential implication in the progression of inflammatory diseases.