title: Characterization and identification of cytochrome P450 metabolites of arachidonic acid released by human peritoneal macrophages obtained from the pouch of Douglas.
abstract: Cytochrome P450 metabolism of arachidonic acid (AA) was investigated in human peritoneal macrophages which play a central role in chronic pelvic diseases in women (for example in endometriosis). The formation of eicosanoids other than prostaglandins (PGs) by these cells is still unknown. In non-activated macrophages obtained from women in the reproductive age, the main [(3)H]-AA metabolites coeluted with epoxyeicosatrienoic acids, dihydroxyeicosatrienoic acids (DHETs) and hydroxyeicosatetraenoic acids (HETEs) in reverse-phase HPLC. After zymosan activation a shift to PGs pathway was observed. Treatment with low doses of 2,3,7,8-tetrachlorodibenzo- p -dioxin increased the formation of a metabolite coeluting with 5,6-DHET. By gas chromatography/mass spectrometry 5,6-DHET (after beta-naphthoflavone induction), and 14,15-DHET as well as 11,12-DHET (after AA stimulation) were identified as major epoxygenase metabolites, respectively. The enantioselective formation of 12(S)-HETE was demonstrated by chiral-phase HPLC. Our findings demonstrate that non-activated peritoneal macrophages produce substantial amounts of bioactive cytochrome P450 metabolites of AA.
authors.affiliation: Department of Obstetrics & Gynecology, University of Freiburg, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Werner
authors.forename: W R
authors.initials: WR
authors.lastname: Schaefer
authors.forename: H
authors.initials: H
authors.lastname: Schweer
authors.forename: W R
authors.initials: WR
authors.lastname: Deppert
authors.forename: U
authors.initials: U
authors.lastname: Karck
authors.forename: H P
authors.initials: HP
authors.lastname: Zahradnik
mesh_terms: D016718:Arachidonic Acid / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004312:Douglas' Pouch / Q000473:pathology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D007553:Isotope Labeling; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism*; D008968:Molecular Conformation
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System