Iron depletion: a defense against intracellular infection and neoplasia

Macrophages and other host cells activated by interferon-gamma (IFN-gamma) can be induced to form a flavoprotein that converts L-arginine to nitric oxide+L-citrulline. Nitric oxide causes efflux of non-heme iron from neoplastic and infected host cells. In the absence of L-arginine, IFN-gamma-induced infected cells can lower their net uptake of iron. Cellular depletion of the metal via either mechanism suppresses DNA synthesis as well as the functioning of aerobic respiratory enzymes. Macrophage regulation of growth of other host cells during embryogenesis, immune responses, or immunosurveillance might involve iron depletion.