Human macrophages degrade tryptophan upon induction by interferon-gamma |
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| Authors: | E R Werner G Bitterlich D Fuchs A Hausen G Reibnegger G Szabo M P Dierich H Wachter |
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| Institution: | 1. Institute for Medical Chemistry and Biochemistry, Austria;1. Institute for Hygiene, University of Innsbruck, Fritz Preglstr. 3, A-6020 Innsbruck, Austria;1. University of Chicago, Department of Medicine, Section of Gastroenterology, Chicago, IL, United States;2. University of Chicago, Department of Human Genetics, Chicago, IL, United States;1. Department of Biomedical Science, University of Sassari, Sassari, Italy;2. National Laboratory of Gender Medicine of the National Institute of Biostructures and Biosystems, Osilo, Sassari, Italy;3. Gynaecologic and Obstetric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy;4. Dipartimento Politiche della Persona Regione Basilicata,Italy;1. Labex Transplantex, Translational Medecine Federation, University of Strasbourg, Strasbourg, France;2. Lung Transplantation Group, University Hospital Strasbourg, Strasbourg France;3. EA 7293 SVTT ‘Stress Vasculaire et Tissulaire en Transplantation’, Translational Medecine Federation, University of Strasbourg, Strasbourg, France;4. UMR CNRS 7213, Biophotonique and Pharmacology Laboratory, Pharmacology School, University of Strasbourg, Strasbourg, France |
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| Abstract: | Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of resting T-cells were found to induce tryptophan degradation by macrophages, the active principle being neutralized by an antiserum for interferon-gamma. Thus phytohemagglutinin acts by activating T-cells to release interferon-gamma which in turn induces macrophages to degrade tryptophan. In all experiments the appearance of neopterin in the culture media was correlated to the observed tryptophan degradation. |
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