Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1950149 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2006 | 9 Pages |
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) D2 and leukotriene (LT) C4 generation. Activation of BMMC by SCF, IL-1β and IL-10 elicits a delayed phase of PGD2 generation dependent on cyclooxygenase (COX) 2 induction. Cytosolic phospholipase A2 α provides arachidonic acid in both phases and amplifies COX-2 induction. Pharmacological experiments implicate an amplifying role for secretory (s) PLA2. We used mice lacking the gene encoding group V sPLA2 (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 PGD2 generation after activation with SCF or with IgE and antigen, while LTC4 generation was not modified. Delayed-phase PGD2 generation and COX-2 induction were reduced ∼35% in C57BL/6 Pla2g5−/− BMMC and were restored by exogenous PGE2. There was no deficit in either phase of eicosanoid generation by Pla2g5−/− BMMC on a BALB/c background. Thus, group V sPLA2 amplifies COX-2 expression and delayed phase PGD2 generation in a strain-dependent manner; it has at best a limited role in immediate eicosanoid generation by BMMC.