Group V secretory phospholipase A 2 amplifies the induction of cyclooxygenase 2 and delayed prostaglandin D 2 generation in mouse bone marrow culture-derived mast cells in a strain-dependent manner

Abstract

Activation of mouse bone marrow-derived mast cells (BMMC) with stem cell factor (SCF) or IgE and antigen elicits exocytosis and an immediate phase of prostaglandin (PG) D 2 and leukotriene (LT) C 4 generation. Activation of BMMC by SCF, IL-1β and IL-10 elicits a delayed phase of PGD 2 generation dependent on cyclooxygenase (COX) 2 induction. Cytosolic phospholipase A 2 α provides arachidonic acid in both phases and amplifies COX-2 induction. Pharmacological experiments implicate an amplifying role for secretory (s) PLA 2. We used mice lacking the gene encoding group V sPLA 2 ( Pla2g5−/−) to definitively test its role in eicosanoid generation by BMMC. Pla2g5−/− BMMC on a C57BL/6 genetic background showed a modest reduction in exocytosis and immediate PGD 2 generation after activation with SCF or with IgE and antigen, while LTC 4 generation was not modified. Delayed-phase PGD 2 generation and COX-2 induction were reduced ∼35% in C57BL/6 Pla2g5−/− BMMC and were restored by exogenous PGE 2. There was no deficit in either phase of eicosanoid generation by Pla2g5−/− BMMC on a BALB/c background. Thus, group V sPLA 2 amplifies COX-2 expression and delayed phase PGD 2 generation in a strain-dependent manner; it has at best a limited role in immediate eicosanoid generation by BMMC.