Interferon-gamma-induced degradation of tryptophan by human cells in vitro.
Several human cells were investigated for their ability to degrade tryptophan and to synthesize neopterin upon induction by interferon-gamma (500 units/ml for 48 h). Concentrations of tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, 7,8-dihydroneopterin and neopterin were assessed in the culture supernatants by HPLC. Fibroblasts, A-22 arachnoidea, HK-2351 scalp, T-2346 meningeom and HeLa cervical carcinoma cells but not HL-60 promyelocytic leukaemia cells were found to degrade tryptophan upon induction by interferon-gamma. Tryptophan is converted to kynurenine by fibroblasts, A-22 arachnoidea and HK-2351 scalp cells and to kynurenine and anthranilic acid by HeLa cervical carcinoma and T-2346 meningeom cells. Kynurenine and anthranilic acid always make up more than 82% of the tryptophan degraded. None of these cells synthesizes 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 7,8-dihydroneopterin or neopterin. Human macrophages form 3-hydroxyanthranilic acid and neopterin, but not 3-hydroxykynurenine, beside kynurenine and anthranilic acid upon activation by interferon-gamma. These data indicate that several human cells can be induced by interferon-gamma to degrade tryptophan. The interferon-gamma induced synthesis of 3-hydroxyanthranilic acid and neopterin, however, appears to be restricted to human macrophages. A hypothesis explaining these findings is presented.
D001708:Biopterins / Q000031:analogs & derivatives / Q000032:analysis; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000494:pharmacology*; D007737:Kynurenine / Q000032:analysis; D019798:Neopterin; D014364:Tryptophan / Q000032:analysis*; D062367:ortho-Aminobenzoates / Q000032:analysis
D007202:Indicators and Reagents; D062367:ortho-Aminobenzoates; D001708:Biopterins; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan