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 (m phi) respond to unopsonized zymosan with the production of superoxide anion (O2-). We investigated the involvement of phospholipid turnover in the transduction mechanism for this phenomenon. Zymosan-stimulated m phi 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 O2- 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 E2 (PGE2) inhibited O2- 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/PGE2 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).
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000096:biosynthesis; D011458:Prostaglandins E / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D011458:Prostaglandins E; D013481:Superoxides; D003994:Bucladesine; D015054:Zymosan; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone