C3-mediated release of prostaglandin from human monocytes: evidence for independent regulation of thromboxane and prostaglandin synthesis.
Human mononuclear phagocytes (HMP) lose the capacity to respond to C3b, exogenous arachidonic acid (AA), and other stimuli of arachidonic acid (AA) metabolism when precultured for 24 hours prior to the addition of stimulus. Data presented in this report suggest that this reduced capacity is not due to loss of the cyclooxygenase enzyme, to autoinactivation of cyclooxygenase, or to release by the cells of inhibitors of PGE and TxB2 production. Additional metabolism of PGE or a shift of AA metabolism from the cyclooxygenase pathway to the lipoxygenase pathways does not occur and hence cannot account for the observation. HMP precultured for 24 hours with gamma interferon (IFN-gamma) retain the capacity to metabolize AA in response to subsequent exposure to C3b and LPS. HMP precultured with LPS or C3b respond to exogenous AA, but not to restimulation with LPS or C3b, by releasing PGE and to a lesser extent TxB2. The amounts of PGE and TxB2 produced under these conditions are reversed when compared to HMP treated with IFN-gamma LPS, or C3b at the initiation of culture. These data suggest that the production of TxB2 and PGE may be independently regulated in HMP and that IFN-gamma affects HMP AA metabolism by different mechanisms than LPS or C3b.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000097:blood; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003176:Complement C3 / Q000502:physiology*; D003179:Complement C3b / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008084:Lipoxygenase / Q000097:blood; D010586:Phagocytes / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011453:Prostaglandins / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood*
D001095:Arachidonic Acids; D003176:Complement C3; D008070:Lipopolysaccharides; D011453:Prostaglandins; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003179:Complement C3b; D007371:Interferon-gamma; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases