title: Zymosan-stimulated production of phosphatidic acid by macrophages: relationship to release of superoxide anion and inhibition by agents that increase intracellular cyclic AMP.
abstract: 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).
mesh_terms: 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*
chemical_list: D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D011458:Prostaglandins E; D013481:Superoxides; D003994:Bucladesine; D015054:Zymosan; D013806:Theophylline; D000242:Cyclic AMP; D015232:Dinoprostone