- Objective The present research was designed to study the involvement of ERK and p38 MAP-kinase in cytosolic phospholipase A 2 (cPLA 2 ) and NADPH-oxidase activation by angiotensin II (Ang II) in human neutrophils. Methods NADPH-oxidase activity was measured by reduction of cytochrome C. cPLA 2 activity was measured in cell lysate using sonicated dispersions of 1 -stearoyl-2-[ 14 C]arachidonyl phosphatidylcholine. Cells were incubated with MEK inhibitor UO126 or with p38 MAP-kinase inhibitor SB202190 prior to stimulation with Ang II. Translocation of p47 phox , p67 phox and cPLA 2 and phosphorylation of ERK and p38 MAP-kinase were measured by immunoblot analysis. Results Ang II induced a dose-dependent activation of NADPH oxidase in neutrophils and monocytes as well as in differentiated PLB-985 cells towards neutrophil or monocyte lineages, but not in cPLA 2 -deficient differentiated PLB-985 cells. An immediate activation of both ERK and p38 MAP-kinase and of cPLA 2 was induced by Ang II in human neutrophils. In addition, Ang II induced translocation of the cytosolic oxidase components, detected by translocation of p47 phox , which preceded the translocation of cPLA 2 induced by this agonist. The p38 MAP-kinase inhibitor SB202190 or the MEK-ERK pathway inhibitor UO126 totally inhibited the activation of both NADPH oxidase and cPLA 2 as well as the translocation of cytosolic oxidase components and of cPLA 2 to the membrane fractions. Conclusions These results suggest that either ERK or p38 MAP-kinase are involved in the activation of both cPLA 2 and NADPH oxidase, and that cPLA 2 is required for activation of the NADPH oxidase by Ang II in human neutrophils.