Exogenous type-II phospholipase A2 stimulates prostaglandin synthesis in rat liver-derived BRL-3A cells in the presence of tumor necrosis factor alpha.
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 alpha (TNF alpha) 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 TNF alpha. Furthermore, pretreatment of cells with type-II PLA2 followed by subsequent stimulation by TNF alpha 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 TNF alpha.
Suga
H
H
Faculty of Pharmaceutical Sciences, University of Tokyo.
Murakami
M
M
Kudo
I
I
Inoue
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016718:Arachidonic Acid; D015232:Dinoprostone; D006497:Heparan Sulfate; D010741:Phospholipases A; D054467:Phospholipases A2; D014409:Tumor Necrosis Factor-alpha