326 Arachidonate Metabolites in Macrophages

During the course o f our studies on the lipid composition o f macrophage membranes, it was noted that 25% of the total fatty acid content of this cell was composed of arachidonie acid (20:4)) Similar values have been reported for both rabbit (1) and h u m a n mononuclear phagocytes (2), whereas the fatty acid complement of most other cell types rarely exceeds a few percent. This unusual enrichment with esterified 20:4 has focused attention on the ability of mononuclear phagocytes to produce prostaglandins (PG) from endogenous stores. PG, depending upon their structure, are thought to play a variety of important roles in the initiation and control o f the inf lammatory process (3). It is now well established that mononuclear phagocytes produce PG in response to a variety o f stimuli that perturb their surface membranes. These include phagocytizable particulates such as zymosan (4) and immune complexes (5) or soluble agents such as phorbol myristate acetate and lipopolysaccharide (6, 7). Bonney et al. (4) have reported that the major synthetic product of mouse peritoneal cells is PGE with smaller amounts of 6-oxo-PGFl~ Unfortunately, there is little information concerning the regulation and control o f the oxygenation products o f 20:4. For this reason we have established a group of defined conditions in which we have examined the relationship between phagocytosis and PG synthesis, the localization and fate of 20:4 in the phospholipid pool of resident peritoneal macrophages, and the proportions of other 20:4 products released upon a zymosan challenge.