Uptake and subcellular distribution of cadmium in resting and mitogen-activated lymphocytes and its relationship to a metallothionein-like protein

Abstract

The effects of cadmium on the immune system have been extensively studied, although relatively little is known about the nature of the interaction between cadmium and lymphocytes. We describe studies that examine the uptake and subcellular distribution of cadmium in resting and mitogen-activated mouse splenic lymphocytes exposed to cadmium in vitro. Mitogen activation was associated with an increased uptake and altered subcellular distribution of cadmium, compared to resting (nonmitogen-activated) lymphocytes. In both resting and mitogen-activated lymphocytes the total uptake of cadmium was concentration-dependent. However, compared to resting lymphocytes, in mitogen-activated lymphocytes, cadmium tended to distribute out of the nuclear and into the cytoplasmic fraction. The Sephadex G-75 exclusion chromatography profile revealed the presence of a cadmium-binding protein eluting identically to metallothionein in mitogen-activated, but not in resting, lymphocytes. The presence of this protein in mitogen-activated lymphocytes is consistent with the differences in subcellular distribution of cadmium reported. Further, the difference between resting and mitogen-activated lymphocytes in the production of this protein, and the known genetic differences in the metallothionein inducibility, may explain some of the reported variability in the effects of cadmium on the immune system.