title: Altered arachidonic acid metabolism during differentiation of the human monoblastoid cell line U937.
abstract: The human cell line U937 was used as a model for differentiation along the mononuclear phagocyte lineage. Following treatment with the phorbol ester TPA, PGE2 and TxB2 secretion was induced 50-100-fold, and both PGF2 alpha and PGI2 levels became detectable in the supernatant of TPA-differentiated U937 cells. The content of the prostaglandin precursor, arachidonic acid, remained unchanged in the cellular phospholipids of undifferentiated and TPA-differentiated U937 cells. Of the enzymes involved in the availability and metabolism of arachidonic acid, phospholipase A2 activity was increased 2-fold in the membranes of TPA-differentiated U937 cells, whereas lysophosphatide acyltransferase activity remained unaltered. Cyclooxygenase activity, however, was enhanced 5-10-fold, which was due to enhanced expression of the enzyme as demonstrated by dot-blot analysis. The data suggest that the capacity to secrete prostaglandins is acquired during differentiation with TPA and results mainly from an increased cyclooxygenase activity. Despite the capacity of TPA-differentiated U937 cells to synthesize prostaglandins, none of the known monocytic stimuli further stimulated prostaglandin secretion in TPA-differentiated U937 cells. Generation of leukotrienes appears to represent a later state in the differentiation along the monocyte-macrophage lineage, since neither LTB4 nor cysteinyl-leukotrienes were detectable in the supernatants of either undifferentiated or TPA-differentiated U937 cells.
authors.affiliation: Department of Pharmacology and Toxicology, Medical School Hannover, F.R.G.
authors.forename: L
authors.initials: L
authors.lastname: Koehler
authors.forename: R
authors.initials: R
authors.lastname: Hass
authors.forename: K
authors.initials: K
authors.lastname: Wessel
authors.forename: D L
authors.initials: DL
authors.lastname: DeWitt
authors.forename: V
authors.initials: V
authors.lastname: Kaever
authors.forename: K
authors.initials: K
authors.lastname: Resch
authors.forename: M
authors.initials: M
authors.lastname: Goppelt-Struebe
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000032:analysis; D015289:Leukotrienes / Q000096:biosynthesis; D008084:Lipoxygenase / Q000032:analysis; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011453:Prostaglandins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D005227:Fatty Acids; D015289:Leukotrienes; D010743:Phospholipids; D011453:Prostaglandins; D016718:Arachidonic Acid; D008084:Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D013755:Tetradecanoylphorbol Acetate