Zymosan‐Stimulated Production of Phosphatidic Acid by Macrophages: Relationship to Release of Superoxide Anion and Inhibition by Agents That Increase Intracellular Cyclic AMP

Murine peritoneal macrophages (mΦ) respond to unopsonized zymosan with the production of superoxide anion (O 2 ‐ ). We investigated the involvement of phospholipid turnover in the transduction mechanism for this phenomenon. Zymosan‐stimulated mΦ produced increased amounts of phosphatidic acid (PA); the increase was first detected at 1.5 min and continued for 10 min of incubation. Production of O 2 ‐ was not detected until between 2 to 4 min after stimulation, and continued to increase through 60 min. Inhibition experiments suggested that these two processes were linked. Theophylline (theo)/ dibutyrylcyclic AMP (dbcAMP) and theo/prostaglandin E 2 (PGE 2 ) inhibited O 2 ‐ production at every time point (79% and 80% inhibition, respectively, at 4 min). Corresponding inhibition of PA production was also achieved at every time point (85% by theo/dbcAMP; 67% by theo/PGE 2 at 4 min). These results are compatible with a role for phospholipid remodeling in the transduction process associated with the respiratory burst. Results suggest that the phospholipid species could be phosphatidylcholine (PC) as well as phosphatidylinositol (PI).