Cytosolic phospholipase A(2) is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells

We have used mice in which the gene for cytosolic phospholipase A(2) (cPLA(2)) has been disrupted to demonstrate the absolute requirement for cPLA(2) in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA(2) prevented the provision of arachidonic acid substrate for biosynthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide synthase 1 in the immediate phase of prostaglandin (PG) D(2) generation. These defects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytosis of β-hexosaminidase. Whereas cPLA(2) is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD(2) generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD(2).