Neopterin modulates toxicity mediated by reactive oxygen and chloride species

FEBS Letters

Werner, Ernst R.¹  Weiss, Günter¹  Fuchs, Dietmar¹  Reibnegger, Gilbert¹  Semenitz, Erich²  Werner-Felmayer, Gabriele¹  Dierich, Manfred P.²  Wachter, Helmut¹  Hausen, Arno¹ 

[1] Institute for Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Hygiene, University of Innsbruck, A-6020 Innsbruck, Austria

关键词: Neopterin;    Antimicrobial toxicity;    Macrophage;    Hydrogen peroxide;    Chloramine;   

DOI  :  10.1016/0014-5793(93)80627-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Neopterin, a pyrazino-pyrimidine derivative, is synthesized in excess by human monocytes/macrophages upon stimulation with interferon-γ, a cytokine derived from activated T-cells. Neopterin is furthermore produced constitutively. A relatively constant ratio between neopterin and its reduced form, 7,8-dihydroneopterin, has been described in human serum. In the study presented here we tested the ability of neopterin and its reduced form to modulate the effects of cytotoxic substances like hydrogen peroxide or hypochlorous acid and N-chloramine derivatives. We show that 7,8-dihydroneopterin potently reduces biological and chemical effects of these substances independently from the pH value. In contrast, at slightly alkaline pH (pH 7.5) neopterin enhances hydrogen peroxide and chloramine-T activity. This is demonstrated by increase of signal intensity in a luminol assay and also by enhancement of toxicity towards bacteria. Thus, the macrophage derived substance neopterin is able both to enhance and to reduce cytotoxicity in dependence of pH value and its oxidation state, and it may have a pivotal role in modulation of macrophage mediated effector mechanism.

【 授权许可】

Unknown