Cyclooxygenase (pghs)-2 dependent prostaglandin (pg) 02 generation in mouse bone marrow-derived mast cells (bmmc) is linked to type ii phospholipase A2 (PLA2)

We have previously demonstrated that BMMC from BALB/cJ mice exhibit biphasic cytokine-dependent and IgE-dependent PGD2 generation; an immediate phase within minutes via PGHS-1, and a delayed phase over hours via PGHS-2. 129/J mice are naturally deficient in functional type II PLA2. BMMC derived from 129/J and BALB/cJ mice were used to investigate the role of type II PLA2 in the two phases of PGD2 generation. PCR amplification and BamH1 digestion of genomic DNA confirmed the presence of a mutated gene for type II PLA2 in 129/J BMMC and not BALB/cJ BMMC. There was no difference in immediate PGD2 release between BMMC from 129/J and BALB/cJ mice. In contrast delayed IgE-dependent and cytokine-dependent PGD2 generation was attenuated 80 to 90% in 129/J BMMC compared to BALB/cJ BMMC (p<0.05). These data indicate an important role for type II PLA2 in providing arachidonic acid as substrate to PGHS-2.