Analysis of the Secretory Phospholipase A2That Mediates Prostaglandin Production in Mast Cells
Journal of Biological Chemistry
Prostaglandin D 2 (PGD 2 ) synthesis in activated mast cells occurs in two phases, an early phase that is dependent on prostaglandin synthase 1 and a delayed phase that is dependent on activation-induced prostaglandin synthase 2 gene expression. Early phase PGD 2 synthesis in activated mast cells also requires the activity of a secretory phospholipase A 2 (PLA 2 ). It has been thought that the secretory PLA 2 expressed in mast cells is group IIa PLA 2 , encoded by the Pla2 g2a gene. However,
... ivated bone marrow-derived mast cells prepared from Pla2 g2a ؉/؉ mice and mast cells prepared from mice with a mutation in the Pla2 g2a gene both demonstrate early phase PGD 2 synthesis. Moreover, mast cells from both murine strains secrete PLA 2 activity following activation. Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that mast cells from Pla2 g2a ؉/؉ and Pla2 g2a ؊/؊ mice do not express group IIa PLA 2 message. Instead, Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that both Pla2 g2a ؉/؉ and Pla2 g2a ؊/؊ mast cells express mRNA for group V PLA 2 , encoded by the Pla2gV gene. An antisense oligonucleotide directed against group V PLA 2 is also able to inhibit both the early phase of PGD 2 production and the secretion of PLA 2 activity by activated mast cells. Our data suggest that (i) group IIa PLA 2 does not play a significant role in murine mast cell prostaglandin synthesis, (ii) group V PLA 2 mediates early mast cell PGD 2 production and transcellular PGE 2 production in murine mast cells, and (iii) much of the data, based on studies with chemical inhibitors and antibodies, suggesting that group IIa PLA 2 is responsible for arachidonic acid mobilization needs to be reevaluated.