- The involvement of Erkl/Erk2 in activation of cytosolic phoshpolipase A-4 (cPL.-\2) and NADPH oxidase by opsonized zymosan (OZ) has been demonstrated by us. However, the present study shows that OZ activates p38 MAP kinase in human neutrophils as well. The relative role of both types of MAP kinase; ERKs and p38 in activation of NADPH oxidase induced by OZ was studied. MEK inhibitor, PD-98059, caused a dose dependent inhibition of su peroxide production induced by 1 mg/ml OZ achieving maximal inhibition of 55 ±6% at 100 mM. SB-303580, p38 MAP kinase specific inhibitor, inhibited Superoxide production in a dose dependent manner reaching maximal inhibition of 52 ±4% at 80 mM. While NADPH oxidase is partially inhibited by either PD-98059 or SB-303580, total inhibition Is achieved when the two inhibitors are combined. These results suggest that both ERKs and p38 are required for activation of NADPH oxidase in human neutrophils by OZ. Based on our previous study demonstrating that cPLA-4 is essential for NADPH oxidase activation, the results of the present study point a role for both ERKs and p38 in cPLAs activation.