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Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FREDERICK MD
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Recent evidence indicates that hypersensitivity reactions, produced in rats by the administration of a protein antigen, alters plasma zinc and iron homeostasis by depressing concentrations of these trace minerals. Studies were performed to determine if hypozincemia occurs as a consequence of redistribution of zinc from plasma to liver by a mechanism involving enhanced hepatic metallothionein MT synthesis. MT, a high cystein-containing cytoplasmic protein, possesses a high affinity for zinc and other heavy metals and has been implicated in zinc homeostasis. Antigen challenge 0.5 mg BSA in rate previously sensitized with either 5 or 10 mg BSA produced a significant decrease in plasma zinc and iron concentrations within 7 hr in an apparent dose-dependent manner. Plasma zinc depression was accompanied by an increase in hepatic MT content as well as MT-associated total Zn and 65 Zn used to pulse-label the metalloprotein. The depression in plasma zinc, but not iron, and the enhanced synthesis of MT was significantly reduced by prior treatment of rats with actinomycin D. This finding suggests a requirement for new mRNA synthesis for zinc, but not iron alterations during hypersensitivity reactions. Results support the concept that induction of hepatic MT may be a common mechanism involved in altered plasma zinc homeostasis regardless of the initiating pathophysiologic condition. Author
APPROVED FOR PUBLIC RELEASE