Open AccessCytosolic phospholipase A2is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells
Author(s) -
Hiroshi Fujishima,
René O. Sanchez Mejia,
Clifton O. Bingham,
Bing Lam,
Adam Sapirstein,
Joseph V. Bonventre,
K. Frank Austen,
P. Jonathan
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.9.4803
Subject(s) - arachidonic acid , prostaglandin d2 , eicosanoid , phospholipase a2 , phospholipase , biology , biochemistry , mast cell , microbiology and biotechnology , prostaglandin , chemistry , immunology , enzyme
We have used mice in which the gene for cytosolic phospholipase A2 (cPLA2 ) has been disrupted to demonstrate the absolute requirement for cPLA2 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 cPLA2 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) D2 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 cPLA2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD2 .