Type II phospholipase A2 is linked to cyclooxygenase-2-mediated delayed prostaglandin D2 generation by cultured mouse mast cells following FcepsilonRI- and cytokine-dependent activation

Abstract

Treatment of murine bone marrow-derived mast cells (BMMC) with interleukin (IL)-10 and IL-1beta increased the expression of type II secretory phospholipase A2 (sPLA2), but not cytosolic PLA2 (cPLA2), after culture for several hours. Further stimulation with IgE and antigen (IgE/Ag) increased cyclooxygenase (COX)-2 expression dramatically, accompanied by augmented delayed prostaglandin (PG) D2 generation over several hours. BMMC were also found to express type IIC PLA2 (PLA2-IIC), a recently described novel sPLA2 possessing 16 cysteine residues, expression of which changed minimally after BMMC activation. Delayed PGD2 generation was suppressed by approximately 80% by an antibody raised against recombinant murine type II sPLA2. These results suggest that, of the three PLA2s expressed in BMMC, type II sPLA2 is the critical enzyme that is coupled with COX-2-dependent PGD2 generation elicited by IgE/Ag in the presence of IL-10 + IL-1beta.