title: Production of prostaglandins, isoprostanes and thromboxane by Aspergillus fumigatus: identification by gas chromatography-tandem mass spectrometry and quantification by enzyme immunoassay.
abstract: Aspergillus fumigatus has been reported to produce prostaglandin (PG)-like substances. The molecular structure of these fungal eicosanoids is however still unknown. By using the gas chromatography-tandem mass spectrometry (GC-MS/MS) methodology we identified a number of eicosanoids that were formed upon incubation of the precursor arachidonic acid ethyl ester (AAE, 10 μM) with three strains of A. fumigatus. The eicosanoids identified include the prostaglandins (PG) PGE(2), 6-keto-PGF(1α) (the stable hydrolysis product of prostacyclin PGI(2)) and PGF(2α), the isoprostanes 15(S)-8-iso-PGF(2α) and 15(S)-8-iso-PGE(2), and thromboxane B(2) (TxB(2), the stable hydrolysis product of TxA(2)). These eicosanoids are identical with those produced by cyclooxygenases (COX) in humans. The biosynthesis of all of these eicosanoids could not be inhibited by the human COX inhibitors indomethacin (100 μM), acetylsalicylic acid (100 μM) or the non-selective human lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid (100 μM). By contrast, the selen-containing antioxidant ebselen (100 μM) was found to inhibit their synthesis. Our results suggest that mammals and fungi employ different eicosanoid biosynthesis pathways. As some of the detected eicosanoids are potent immunomodulators and bronchoconstrictors, they could play a possible role in pulmonary diseases associated with A. fumigatus infection.
authors: Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim of the University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. claudio.kupfahl@t-online.de
authors: Claudio
authors: C
authors: Kupfahl
authors: Dimitrios
authors: D
authors: Tsikas
authors: Jonas
authors: J
authors: Niemann
authors: Gernot
authors: G
authors: Geginat
authors: Herbert
authors: H
authors: Hof
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D001228:Aspergillosis / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000378:metabolism*; D001393:Azoles / Q000494:pharmacology; D015777:Eicosanoids / Q000032:analysis / Q000096:biosynthesis; D004986:Ether / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007124:Immunoenzyme Techniques / Q000379:methods; D054833:Isoindoles; D028421:Isoprostanes / Q000032:analysis / Q000096:biosynthesis*; D016566:Organoselenium Compounds / Q000494:pharmacology; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis*; D053719:Tandem Mass Spectrometry / Q000379:methods; D013931:Thromboxanes / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D001393:Azoles; D015777:Eicosanoids; D054833:Isoindoles; D028421:Isoprostanes; D016566:Organoselenium Compounds; D011453:Prostaglandins; D013931:Thromboxanes; D004986:Ether; D016718:Arachidonic Acid; C042986:ebselen