Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions

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Abstract
Recent evidence indicates that hypersensitivity reactions, produced in rats by the administration of a protein antigen [Ag], alters plasma Zn and Fe homeostasis by depressing concentrations of these trace minerals. Studies were performed to determine if altered Zn homeostasis involves, in part, enhanced hepatic metallothionein (MT) synthesis. MT, a high cysteine-containing cytoplasmic protein, possesses a high affinity for Zn and other heavy metals and is implicated in Zn homeostasis. Ag challenge (0.5 mg BSA [bovine serum albumin]) in rats previously sensitized with 5 or 10 mg BSA produced a significant decrease in plasma Zn and Fe concentrations within 7 h in an apparent dose-dependent manner. Plasma Zn depression was accompanied by an increase in hepatic MT content and MT-associated total Zn and 65Zn used to pulse-label the metalloprotein. The depression in plasma Zn, but not Fe, and the enhanced synthesis of MT was significantly reduced by prior treatment of rats with actinomycin D. New mRNA synthesis may be required for Zn, but not Fe alterations during hypersensitivity reactions. Induction of hepatic MT may be a common mechanism involved in altered plasma Zn homeostasis regardless of the initiating pathophysiologic condition.

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