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 A 2, 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 incorporation 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 A 2 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 A 2 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 A 2 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.
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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