Interaction of zinc ions with human peripheral blood mononuclear cells

Zinc is an important trace element for immune function. The mechanisms by which zinc ions interact with immune cells are, however, still poorly understood. In the present study, we succeeded in defining transferrin and insulin as proteins which selectively enhance zinc-induced monokine induction in peripheral blood mononuclear cells (PBMC). An involvement of the transferrin receptor and the insulin receptor was ruled out. Zinc stimulation of PBMC resulted in an increase of intracellular free zinc, measured by a zinc-specific fluorescence probe, zinquin, the amount of which could be raised by substitution of neither transferrin nor insulin. Inhibition of second messengers by herbimycin A and HA 1004 revealed a participation of protein tyrosine kinases and of cAMP- and cGMP-dependent protein kinases in zinc-induced monokine secretion. We therefore suggest that zinc acts synergistically with stimulants of the above-mentioned signal transduction pathways by direct influence on the second messenger niveau.