A MITOGEN-ACTIVATED PROTEIN-KINASE INDEPENDENT PATHWAY INVOLVED IN THE PHOSPHORYLATION AND ACTIVATION OF CYTOSOLIC PHOSPHOLIPASE A(2) IN HUMAN NEUTROPHILS STIMULATED WITH TUMOR-NECROSIS-FACTOR-ALPHA

Although tumor necrosis factor (TNF)-alpha stimulation of human neutro phils does not result in a significant release of arachidonic acid, it primes the cell for arachidonic acid release when cells are further s timulated by agents that induce an intracellular calcium increase. We demonstrate that TNF-alpha stimulation of neutrophils induces the phos phorylation of cytosolic phospholipase A(2) (cPLA(2)) and also increas es its activity. These results indicate that although TNF-alpha, by it self, does not cause the release of arachidonic acid in intact cells, it increases the phosphorylation and activation of the enzyme cPLA(2). Since we recently found that TNF-alpha stimulation of neutrophils doe s not increase the tyrosine phosphorylation or activation of the p42(e rk2) and p44(erk1) mitogen-activated protein kinases (MAPKs), the pres ent studies demonstrate the involvement of a MAPK independent pathway in the phosphorylation and activation of cPLA(2). (C) 1995 Academic Pr ess,Inc.