Group V secretory phospholipase A2 amplifies the induction of cyclooxygenase 2 and delayed prostaglandin D2 generation in mouse bone marrow culture-derived mast cells in a strain-dependent manner.
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-1beta and IL-10 elicits a delayed phase of PGD(2) generation dependent on cyclooxygenase (COX) 2 induction. Cytosolic phospholipase A(2) alpha 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 approximately 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.
Diaz
Bruno L
BL
Department of Medicine Harvard Medical School and the Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
Satake
Yoshiyuki
Y
Kikawada
Eriya
E
Balestrieri
Barbara
B
Arm
Jonathan P
JP
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D054505:Group V Phospholipases A2; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010741:Phospholipases A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D013045:Species Specificity
D051546:Cyclooxygenase 2; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054467:Phospholipases A2; C516300:Pla2g5 protein, mouse; D015230:Prostaglandin D2