Synthesis of eicosanoids by gamma-interferon-differentiated U937 cells.
Interferons induce morphological, biochemical and functional alterations in monocyte macrophage and myeloid cell lines. We studied the effect of 3 days incubation with gamma-interferon from human buffy coats on the global synthesis of arachidonic acid metabolites by U937 cells. Interferon-induced morphologic changes including cytoplasmic and nuclear changes and the appearance of multiple lysosomal-like granules consistent with cellular differentiation were observed by electron microscopy. The labeling of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine was increased and that of phosphatidylinositol, free fatty acids as 3H-arachidonic acid and neutral lipids reduced, when interferon-treated cells were incubated with 3H-arachidonic acid. Interferon caused qualitative and quantitative changes in the synthesis of cyclooxygenase and lipoxygenase products. A23187, a calcium ionophore, and the tumor promotor, phorbol myristate acetate, greatly increased the synthesis by interferon-differentiated cells of 2 cyclooxygenase products; synthesis of lipoxygenase products was reduced. In the presence of indomethacin, 'shunting' into putative lipoxygenase products occurred. The relationship between interferon-induced morphologic and functional changes, the development of altered phospholipid and eicosanoid metabolism and the identity of these metabolites are yet to be established.
D002454:Cell Differentiation; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D010743:Phospholipids / Q000096:biosynthesis*; D011453:Prostaglandins / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010743:Phospholipids; D011453:Prostaglandins; D007371:Interferon-gamma; D008084:Lipoxygenase; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide