Exogenous group II phospholipase A2 induces prostaglandin E2 production in mouse peritoneal macrophages.
Cultures of mouse peritoneal resident macrophages produced prostaglandin E2 when exposed to extracellular group II phospholipase A2. The response to group II phospholipase A2 was concentration dependent, and prostaglandin E2 production in response to 1 microgram/ml purified group II enzyme was comparable to the maximal response elicited by lipopolysaccharide. Group II phospholipase A2 required millimolar concentrations of extracellular Ca2+ for the induction of prostaglandin E2 production, as well as for phospholipase A2 activity. YM-26734 (4-(3,5-didodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyph eny l) chroman), a selective inhibitor of group II phospholipase A2, inhibited not only the enzyme activity but also the prostaglandin E2 production-inducing activity of group II phospholipase A2 in a concentration-dependent manner. These findings suggest that group II phospholipase A2 released into the extracellular space may induce prostaglandin E2 production through hydrolysis of plasma membrane phospholipids. Taken together with the previous finding that YM-26734 suppressed inflammatory responses in vivo, these results suggest that group II phospholipase A2 may play a role in the excitation and/or progression of inflammatory processes through the production of eicosanoids.
Molecular Medicine Research Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
A
A
Miyake
H
H
Yamamoto
T
T
Enomori
H
H
Kawashima
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D006868:Hydrolysis; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism
D002839:Chromans; D010636:Phenols; D010743:Phospholipids; C084181:YM 26734; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D002118:Calcium