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(Received for publication, October 17, 1996)
From the Departments of Biological Chemistry and Molecular and
Medical Pharmacology, and the Molecular Biology Institute, UCLA Center
for the Health Sciences, Los Angeles, California 90095
Aggregation of IgE cell surface receptors on
MMC-34 cells, a murine mast cell line, induces the synthesis and
secretion of prostaglandin D2 (PGD2). Synthesis
and secretion of PGD2 in activated MMC-34 cells occurs in
two stages, an early phase that is complete within 30 min after
activation and a late phase that reaches a maximum about 6 h after
activation. The early and late phases of PGD2 generation
are mediated by prostaglandin synthase 1 (PGS1) and prostaglandin
synthase 2 (PGS2), respectively. Arachidonic acid, the substrate for
both PGS1 and PGS2, is released from membrane phospholipids by the
activation of phospholipases. We now demonstrate that in activated mast
cells (i) secretory phospholipase A2 (PLA2) mediates the release of arachidonic acid for early,
PGS1-dependent synthesis of PGD2; (ii)
secretory PLA2 does not play a role in the late,
PGS2-dependent synthesis of PGD2; (iii)
cytoplasmic PLA2 mediates the release of arachidonic acid
for late, PGS2-dependent synthesis of PGD2; and
(iv) a cytoplasmic PLA2-dependent step precedes
secretory PLA2 activation and is necessary for optimal PGD2 production by the secretory
PLA2/PGS1-dependent early pathway.
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