Open AccessFunctional coupling between secretory phospholipase A2and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A2
Author(s) -
Jesús Balsinde,
Marı́a A. Balboa,
Edward A. Dennis
Publication year - 1998
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.95.14.7951
Subject(s) - phospholipase a2 , phospholipase a , arachidonic acid , cytosol , phospholipase , cyclooxygenase , lipid signaling , platelet activating factor , stimulation , microbiology and biotechnology , prostaglandin , biology , lipopolysaccharide , eicosanoid , biochemistry , chemistry , enzyme , endocrinology
Secretory phospholipase A2 (sPLA2 ) is the major effector involved in arachidonic acid (AA) mobilization and prostaglandin E2 (PGE2 ) production during stimulation of P388D1 macrophages with the inflammatory stimuli bacterial lipopolysaccharide and platelet-activating factor. We herein demonstrate that PGE2 in stimulated P388D1 cells is accounted for by the inducible cyclooxygenase (COX)-2. COX-1, though present, appears not to participate significantly in stimulus-induced PGE2 production in P388D1 macrophages. Reconstitution experiments utilizing exogenous recombinant sPLA2 demonstrate that activation of the sPLA2 at the plasma membrane is highly dependent on previous activation of the cytosolic phospholipase A2 (cPLA2 ). Collectively these results demonstrate (i ) that functional coupling exists between sPLA2 and COX-2 in activated cells, (ii ) the critical role that cPLA2 plays in lipid mediator production, and (iii ) that there is crosstalk between cPLA2 and sPLA2 in the cell.