Interferon‐gamma independent oxidation of melatonin by macrophages

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Abstract
Mononuclear phagocytes appear to synthesize kynurenine‐like products from the oxidation of biologically active indole compounds including melatonin, catalyzed by interferon (IFN)‐γ‐inducible enzyme indoleamine 2,3‐dioxygenase (IDO). Concanavalin A (Con A) is a plant lectin that induces interferon‐gamma (IFN‐γ) production by T cells. In this study we investigated whether Con A‐primed peritoneal macrophages are able to oxidize melatonin to N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK). The AFMK production was accompanied by chemiluminescence. It was found that Con A‐primed but not resident macrophages produce AFMK. Surprisingly, Con A‐primed macrophages from IFN‐γ‐deficient mice were as effective as macrophages from IFN‐γ‐sufficient mice in oxidizing melatonin. Moreover, addition of an inhibitor of IDO (1‐methyltryptophan) did not affect melatonin oxidation. Con A‐primed but not resident macrophages have a significant content of myeloperoxidase (MPO) and inhibition of MPO by azide completely blocked chemiluminescence and AFMK production. Thus, our findings provide evidence that melatonin oxidation by macrophages may occur through a mechanism dependent of MPO and independent of IFN‐γ and IDO activity.

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