title: Pathways for arachidonic acid mobilization in zymosan-stimulated mouse peritoneal macrophages.
abstract: Resident peritoneal macrophages release arachidonic acid when challenged by zymosan, a phagocytosable particle. The present study was designed to investigate the pathways for arachidonic acid mobilization in zymosan-stimulated macrophages. Experiments were conducted with [3H]arachidonic acid-labeled macrophages to establish the relative contribution of acyltransferases, phospholipase A2, and diacylglycerol lipase to overall arachidonic acid release. Upon zymosan stimulation, [3H]arachidonic acid incorporation into phospholipids was significantly enhanced. Stimulus-induced activation of arachidonic acid incorporated was not observed immediately, but was found 5 min after cell challenge. On the other hand, the results indicated a rapid accumulation of intracellular free [3H]arachidonic acid that paralleled the appearance of both [3H]glycerol-labeled lysophosphatidylcholine and [3H]glycerol-labeled lysophosphatidylinositol, the by-products of phospholipase A2 action on phosphatidylcholine and phosphatidylinositol, respectively. A transient accumulation of [3H]arachidonate-carrying diacylglycerol was also observed. However, no appreciable alterations in the levels of [3H]monoacylglycerol were found. The phospholipase A2 inhibitor nordihydroguaiaretic acid substantially prevented the zymosan-induced arachidonic acid release. In contrast, RHC 80267, a diacylglycerol lipase inhibitor, though preventing diacylglycerol breakdown, did not have any effect on [3H]arachidonic acid release From these results, it is concluded that: (1) the phospholipase A2 pathway controls arachidonic acid release upon zymosan stimulation; (2) the diacylglycerol lipase pathway appears not to be involved in arachidonic acid release by stimulated cells; (3) the acyltransferases play a remarkable role in controlling free arachidonic acid levels, but they do not participate in the increase of free fatty acid levels observed upon cell stimulation.
authors.affiliation: Centro de Investigación del Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Balsinde
authors.forename: B
authors.initials: B
authors.lastname: Fernández
authors.forename: J A
authors.initials: JA
authors.lastname: Solís-Herruzo
authors.forename: E
authors.initials: E
authors.lastname: Diez
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D010537:Peritoneum; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D003512:Cyclohexanones; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D009637:Masoprocol; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D015054:Zymosan; D000217:Acyltransferases; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2