Regulation of arachidonic acid metabolites in macrophages

Abstract

The lipids of mouse peritoneal macrophages contain high levels (25 mole percent) of esterified arachidonic acid (20:4). Following in vitro exposure to unopsonized zymosan, these cells synthesize and release oxygenated products of 20:4. Maximal levels of zymosan ingestion promote the release of 40-50% of the 20:4 content of cultures without loss of viabilitiy. Release of radiolabel from macrophages prelabeled with [3H]20:4 provides a quantitative measure for the synthesis of 20:4-derived products. Approximately 67% of the released 20:4 is recovered as prostaglandins (PG) (51% PGE and 16% 6-oxo-PGF1 alpha) and the remainder as apolar products tentatively identified as hydroxy-eicosatetraenoic acids. The kinetics of synthesis are comparable for both sets of products. A detailed examination of PGE synthesis indicated the PGE levels rise in parallel with phagocytosis during a continuous exposure of macrophages to zymosan. The concentration of particles determines the initial rate of PGE release, but the time-course of synthesis is finite (approximately 60 min), regardless of the zymosan dose. These observations are compatible with the notion that phagocytosis results in a burst of PG synthesis, the size of which is determined by the phagocytic stimulus. This is supported by the finding that secondary challenges of zymosan promote new rounds of PG synthesis by macrophages.