PMID- 10897414 OWN - NLM STAT- MEDLINE DCOM- 20001016 LR - 20180815 IS - 0065-2598 (Print) IS - 0065-2598 (Linking) VI - 479 DP - 2000 TI - Activation of cytosolic phospholipase A2 by opsonized zymosan in human neutrophils requires both ERK and p38 MAP-kinase. PG - 115-23 AB - The present study demonstrates that stimulation of human neutrophils with opsonized zymosan (OZ), which binds to Fc gamma receptors (Fc gamma Rs) and C3b receptors, activates both ERK and p38 MAP-kinase. Thus, the relative role of both types of MAP-kinase, ERK and p38, in activation of cPLA2 by OZ was studied. cPLA2 activation by OZ was detected 15 sec after stimulation, maintained a plateau for 10 min and decreased thereafter. p38 MAP-kinase activation exhibited kinetics similar to that of cPLA2, while ERK activation was detected within 15 sec but decreased significantly in less than 5 min after stimulation. Pretreatment of the cells with the MEK inhibitor, PD-098059, or the p38 MAP-kinase inhibitor, SB-203580 resulted in total inhibition of ERK or p38 MAP-kinase activity, respectively. Each inhibitor caused a partial inhibition during the time course of cPLA2 activity, while their combination caused a total inhibition. Compared to OZ, inactivated OZ, which does not contain the complement proteins, induced an identical time-dependent stimulation of ERK and p38 MAP-kinase as well as a similar cPLA2 activity, suggesting that the role of the C3b receptors in this system is negligible. It is concluded that OZ activates both ERK and p38 MAP-kinase and that the two isotypes are required for the onset and maintenance of cPLA2 activity. FAU - Hazan-Halevy, I AU - Hazan-Halevy I AD - Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University, Negev and Soroka Medical Center, Beer-Sheva, Israel. FAU - Levy, R AU - Levy R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Adv Exp Med Biol JT - Advances in experimental medicine and biology JID - 0121103 RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) RN - OU13V1EYWQ (SB 203580) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Cytosol/enzymology MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Humans MH - Imidazoles/pharmacology MH - Kinetics MH - Mitogen-Activated Protein Kinases/*blood MH - Neutrophils/*enzymology MH - Phospholipases A/*blood MH - Phospholipases A2 MH - Pyridines/pharmacology MH - p38 Mitogen-Activated Protein Kinases EDAT- 2000/07/18 11:00 MHDA- 2000/10/21 11:01 CRDT- 2000/07/18 11:00 PHST- 2000/07/18 11:00 [pubmed] PHST- 2000/10/21 11:01 [medline] PHST- 2000/07/18 11:00 [entrez] AID - 10.1007/0-306-46831-X_10 [doi] PST - ppublish SO - Adv Exp Med Biol. 2000;479:115-23. doi: 10.1007/0-306-46831-X_10.