Exogenous Type-II Phospholipase A₂ Stimulates Prostaglandin Synthesis in Rat Liver-Derived BRL-3A Cells in the Presence of Tumor Necrosis Factor α

抄録

The effect of extracellular type-II phospholipase A₂ (PLA₂) on prostaglandin (PG) synthesis has been studied using rat liver-derived BRL-3A cells. The addition of type-II PLA₂ to the medium of BRL-3A cells resulted in a marked decrease in the enzymatic activity in the medium. An immunochemical study involving an anti-(type-II PLA₂) antibody revealed that a significant amount of PLA₂ was attached to the surface of type-II PLA₂-treated BRL-3A cells. Heparin inhibited the binding of PLA₂ almost completely. Only modest release of PGE₂ over the control value was observed when cells were treated with PLA₂ alone or tumor necrosis factor α (TNFα) alone, whereas PGE₂ production as well as arachidonic acid release from phospholipids was augmented more than additively in the presence of both type-II PLA₂ and TNFα. Furthermore, pretreatment of cells with type-II PLA₂ followed by subsequent stimulation by TNFα caused an appreciable increase in PGE₂ production. Thus, type-II PLA₂ bound to cell-surface heparin-like molecules may exert its activity and participate in eicosanoid generation only in the presence of TNFα.