Macrophage migration inhibitory factor (MIF)--its role in catecholamine metabolism

Macrophage migration inhibitory factor (MIF) was originally identified several decades ago as a lymphokine-derived protein that inhibited monocyte migration. Recently, it has been reported that MIF has D-dopachrome tautomerase, phenylpyruvate tautomerase and thiol protein oxidoreductase activities, although the physiological significance of those activities is not yet clear. Here we show that MIF is able to catalyze the conversion of dopaminechrome and norepinephrinechrome, toxic quinone products of the neurotransmitters dopamine and norepinephrine, respectively, to indole derivatives that may serve as precursors to neuromelanin. Since MIF is highly expressed in human brain, these observations raise the possibility that MIF participates in a detoxification pathway for catecholamine products and could therefore have an important role for neural tissues. The potential role of MIF in the formation of neuromelanin from catecholamines is also an extremely interesting possibility.