NONPROTECTIVE EFFECTS OF EXTRACELLULAR METALLOTHIONEIN

Metallothionein (MT) is a small, cysteine-rich protein that is readily induced by exposure to heavy metal cations. In previous work, we have demonstrated that MT has several significant immunomodulatory propert ies. MT decreases antigen-specific humoral responses in vivo and inhib its the ability of T cells to proliferate in response to antigen prese nted in vitro. To further characterize the mechanism by which this pro tein inhibits responsiveness to antigen, we have examined the effects of MT on cell viability in an antigen-presentation assay. MT (20 mu M) caused substantial death to both lymphocytes and monocytes after 3 da ys of culture. The observed toxicity cannot be attributed to either in creased superoxide radical generation or to production of tumor necros is factor by MT-treated macrophages. Fractionation of supernatants fro m MT-treated cells suggests that the agent responsible for causing cyt otoxicity is a soluble factor of at least 30 kDa. These results counte r the perception that metallothionein uniformly plays a protective rol e in metal-stressed individuals. (C) 1996 Academic Press, Inc.