Functional coupling between secretory phospholipase A(2) and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A(2)

Secretory phospholipase A(2) (sPLA(2)) is the major effector involved in arachidonic acid (AA) mobilization and prostaglandin E(2) (PGE(2)) production during stimulation of P388D(1) macrophages with the inflammatory stimuli bacterial lipopolysaccharide and platelet-activating factor. We herein demonstrate that PGE(2) in stimulated P388D(1) cells is accounted for by the inducible cyclooxygenase (COX)-2. COX-1, though present, appears not to participate significantly in stimulus-induced PGE(2) production in P388D(1) macrophages. Reconstitution experiments utilizing exogenous recombinant sPLA(2) demonstrate that activation of the sPLA(2) at the plasma membrane is highly dependent on previous activation of the cytosolic phospholipase A(2) (cPLA(2)). Collectively these results demonstrate (i) that functional coupling exists between sPLA(2) and COX-2 in activated cells, (ii) the critical role that cPLA(2) plays in lipid mediator production, and (iii) that there is crosstalk between cPLA(2) and sPLA(2) in the cell.