Regulation of the oxidative burst of macrophages by lipid mediators.
Macrophages, on stimulation, generate both cyclo-oxygenase and lipoxygenase products of arachidonic acid as well as the acetylated phospholipid, PAF-acether. The latter induces the oxidative burst in C. parvum-activated macrophages, but has little activity on resident macrophages. Mouse macrophages are generally rather insensitive to PAF-acether. Prostaglandin (PG)E2, on the other hand is a potent inhibitor of the macrophage oxidative burst, though its activity is also dependent upon the source of the macrophages and the stimulus used. Several lipoxygenase inhibitors inhibit the oxidative burst of mouse peritoneal macrophages, while other authors have reported stimulatory effects of lipoxygenase products on different macrophage populations. The differential actions of lipoxygenase and cyclo-oxygenase products on the macrophage oxidative burst are reflected by the effect of arachidonic acid on the zymosan induced response of mouse resident peritoneal cells: initial enhancement, followed by prolonged inhibition, the latter being indomethacin-sensitive. While PAF-acether is probably an important initiator of the macrophage oxidative burst in vivo, arachidonic acid modulates the response by a "see-saw mechanism", lipoxygenase products being stimulatory and cyclo-oxygenase products (mainly PGE2) being inhibitory.
D000818:Animals; D006168:Guinea Pigs; D008055:Lipids / Q000502:physiology*; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology
D008055:Lipids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011458:Prostaglandins E; C026613:1-0-octadecyl 2-0-acetyl sn-glycero-3-phosphorylcholine; D008084:Lipoxygenase