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.
Weinberg
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Department of Biology, Indiana University, Bloomington 47405.
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism; D004261:DNA Replication; D007371:Interferon-gamma; D007501:Iron / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010272:Parasitic Diseases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D007501:Iron