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 bo ne marrow-derived mast cells. For the immediate phase, quantitative analysi s of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA(2) prevented the provision of arachidonic acid substrate for biosy nthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide syntha se 1 in the immediate phase of prostaglandin (PG) D-2 generation. These def ects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytos is of beta-hexosaminidase, Whereas cPLA(2) is essential for immediate eicos anoid generation by providing arachidonic acid, its role in delayed-phase P GD(2) generation is more complex and involves the activation dependent indu ction of prostaglandin endoperoxide synthase 2 and the supply of arachidoni c acid for metabolism to PGD(2).