Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2S (groups III and XII)

Here we report cellular arachidonate (AA) release and prostaglandin (PG) production by novel classes of secretory phospholipase A2s (sPLA2s), groups III and XII. Human group III sPLA2 promoted spontaneous AA release, which was augmented by interleukin-1, in HEK293 transfectants. The central sPLA2 domain alone was sufficient for its in vitro enzymatic activity and for cellular AA release at the plasma membrane, whereas either the unique N- or C-terminal domain was required for heparanoid-dependent action on cells to augment AA release, cyclooxygenase-2 induction, and PG production. Group III sPLA2 was constitutively expressed in two human cell lines, in which other sPLA2s exhibited different stimulus inducibility. Human group XII sPLA2 had a weak enzymatic activity in vitro and minimally affects cellular AA release and PG production. Cells transfected with group XII sPLA2 exhibited abnormal morphology, suggesting a unique functional aspect of this enzyme. Based on the present results as well as our current analyses on the group I/II/V/X sPLA2s, general properties of cellular actions of a full set of mammalian sPLA2s in regulating AA metabolism are discussed.