Release of prostaglandin D₂ by murine mast cells: importance of metabolite formation for antiproliferative activity

Abstract

Prostaglandin (PG) D₂ , PGJ₂ and Δ¹² -PGJ₂ are antiproliferative eicosanoids. We investigated the production of PGD₂ by murine bone marrow-derived mast cells (BMMC) taking into consideration metabolism of PGD₂ to PGD₂ and Δ¹²-PGJ₂. PG-metabolites were quantified by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). Stimulated with calcium ionophore A23187 BMMC released eight-fold more PGJ₂ and Δ¹²-PGJ₂ than PGD₂. Conversion of endogenously produced PGD₂ to PGJ₂ and Δ¹²-PGJ₂ proceeded rapidly in contrast to metabolism of exogenously added PGD₂. The antiproliferative potency of these prostaglandins is demonstrated in vitro. We conclude that determination of PGD₂ production by mast cells must take into consideration rapid conversion to active derivatives, which may play a significant role in growth regulation.