Interleukin-one induced arachidonic acid turnover in macrophages

Recombinant Interleukin-1 beta (rIL-1 beta) induced dose-dependent synthesis of PGE2 and activation of both cell-associated and soluble phospholipase A2 (PLA2) in cultured mouse peritoneal macrophages. Kinetic studies showed that rIL-1 beta was able to induce a 2-fold increase in membrane bound PLA2 activity in the cells within 1 hour. Elevated levels of PGE2 were however observed only after 4 hours stimulation of the cells while significant levels of soluble PLA2 activity were observed only after 16 hours stimulation of the cells. Stimulation with rIL-1 beta of macrophage cultures pre-labelled with [14C]arachidonic acid resulted in a loss of label from both phosphatidyl-choline and phosphatidylinositol in only 10 min, which was not observed in control (unstimulated) cultures. These results are indicative that the two phospholipids are the principal source of arachidonic acid for IL-1 induced prostaglandin synthesis.