Cytosolic phospholipase A2 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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-04, Vol.96 (9), p.4803-4807
Main Authors: Fujishima, H, Sanchez Mejia, R O, Bingham, 3rd, C O, Lam, B K, Sapirstein, A, Bonventre, J V, Austen, K F, Arm, J P
Format: Article
Language:English
Subjects:
Animals
Arachidonate 5-Lipoxygenase - metabolism
Biochemistry
Biological Sciences
Bone marrow
Bone Marrow Cells - metabolism
Cells
Cells, Cultured
Cytosol - metabolism
Eicosanoids - biosynthesis
Gene Expression Regulation
Mast Cells - metabolism
Mice
Mice, Knockout
Phospholipases A - genetics
Phospholipases A - metabolism
Phospholipases A2
Rodents
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Summary: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 .
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.9.4803