Phosphorylation of cytosolic phospholipase A(2) and the release of arachidonic acid in human neutrophils

Kinases mediating phosphorylation and activation of cytosolic phospholipase A(2) (cPLA(2)) in intact cells remain to be fully characterized. Platelet- activating factor stimulation of human neutrophils increases cPLA(2) phosph orylation, This increase is inhibited by PD 98059, a mitogen-activated prot ein (MAP)/extracellular signal-regulating kinase (erk) 1 inhibitor, but not by SE 203580, a p38 MAP kinase inhibitor, indicating that this action is m ediated through activation of the p42 MAP kinase (erk2), However, platelet- activating factor-induced arachidonic acid release is inhibited by both PD 98059 and SE 203580, Stimulation by TNF-alpha increases cPLA(2) phosphoryla tion, which is inhibited by SE 203580, but not PD 98059, suggesting a role for p38 MAP kinase, LPS increases cPLA(2) phosphorylation and arachidonic a cid release. However, neither of these actions is inhibited by either PD 98 059 or SE 203580, PMA increases cPLA(2) phosphorylation. This action is inh ibited by PD 98059 but not SE 203580. Finally, FMLP increases cPLA(2) phosp horylation and arachidonic acid release. Interestingly, while the FMLP-indu ced phosphorylation of cPLA(2) is not affected by the inhibitors of the p38 MAP kinase or erk cascades, both inhibitors significantly decrease arachid onic acid release stimulated by FMLP, SE 203580 or PD 98059 has no inhibito ry effects on the activity of coenzyme A-independent transacylase.