RELEASE OF PROSTAGLANDIN D-2 BY MURINE MAST-CELLS - IMPORTANCE OF METABOLITE FORMATION FOR ANTIPROLIFERATIVE ACTIVITY

PROSTAGLANDIN (PG) D-2, PGJ(2) and Delta(12)-PGJ(2), are antiprolifera tive eicosanoids. We investigated the production of PGD(2) by murine b one marrow-derived mast cells (BMMC) taking into consideration metabol ism of PGD(2) to PGD(2) and Delta(12)-PGJ(2). PG-metabolites were quan tified by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). Stimulated with calcium ionophore A23187 BMMC released eight-fold more PGJ(2) and Delta(12)-PGJ(2) than PGD(2). Conv ersion of endogenously produced PGD, to PGJ, and Delta(12)-PGJ(2) proc eeded rapidly in contrast to metabolism of exogenously added PGD(2). T he antiproliferative potency of these prostaglandins is demonstrated i n vitro. We conclude that determination of PGD, production by mast cel ls must take into consideration rapid conversion to active derivatives , which may play a significant role in growth regulation.