Abstract
Upon stimulation with interferon-γ, a typical Thl cell-derived cytokine, human monocyte-dertved macrophages produce neopterin derivatives and in parallel degrade the essential amino acid L-tryptophan to L-kynurenine and subsequently to 3-hydroxyanthramlic acid and anthramlic acid. In parallel, stimulated macrophages produce reactive oxygen species such as hydrogen peroxide and hypochlorous acid. Earlier, neopterin and 7.8-dihydroneoptenn were found to enhance or decrease effects of reactive oxygen species in vitro, depending on concentration and on environmental condition. In this study, we investigated the ability of tryptophan and its metabolites to interfere with radicals in vitro by means of a chemiluminiseence-based assay system. When using hydrogen peroxide or chloramine Τ as source for radical formation. L-tryptophan and its catabolites reduced chennluminescence according to a dose-response relationship, 3-hydroxvanthranilic acid being the most efficient compound. Apart from L-kynurenme the scavenging effects of tryptophan and its metabolites were not affected by changes m pH from 5.5 to 7.5. Our data indicate that tryptophan degradation produces metabolites with a high scavenging ability for reactive oxygen and chlorine species, thereby establishing a self-regulatory mechanism to limit the tissue damage by reactive radicals produced by macrophages.
© 2013 by Walter de Gruyter GmbH & Co.
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
