Induction of metallothionein by a macrophage factor and the partial characterization of the factor.

The mechanism of metallothionein (MT) induction by lipopolysaccharide (LPS) was studied using an in vitro system. Rat peritoneal macrophages were incubated with or without LPS, after which the incubation medium was overlaid on human hepatic (Chang) cells. MT synthesis was induced in Chang cells treated with the macrophage medium incubated with LPS. No induction was observed when LPS was added directly to the Chang cell medium or when Chang cells were treated with the macrophage medium incubated without LPS. These results suggest that induction of MT by LPS is mediated by a factor released from macrophages. The factor is different from the known primary inducers of MT, such as heavy metals, glucocorticoid hormones, interleukin 1, and interferon. The factor is heat stable, nondialyzable, and stable at pH 2. Although its activity is lost by pepsin and trichloroacetic acid, it is resistant to trypsin.