Intracellular zinc during cell activation and zinc deficiency

Zinc is an essential trace element having manifold functions within living cells. Zinc deficiency but also zinc excess impairs cell-specific functions whereas a balanced zinc level is required for an adequate cell behavior.

This study deals with the impact of cellular priming due to stimulation with interleukin (IL)-1, IL-2, IL-4, IL-6 or the chemokine CXCL12a and its subsequent influence on the intracellular free zinc concentration. Since cellular priming and activation is essential for proper immunological reactions, and across that highly cell-type specific, we investigated T cells, B cells, and peripheral blood mononuclear cells (PBMCs). Additionally, alterations of the intracellular zinc content was investigated by inducing zinc deficiency using the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) with subsequent re-supplementation of zinc, hence generating an intracellular zinc flux. Evaluation of zinc staining with FluoZin3-AM, Zinpyr-1 and Zinquin was done by flow cytometry or by fluorescence microscopy.

Our results indicate that cellular priming for different periods of time (10 minutes/one hour) causes decreased intracellular free zinc concentrations in the FluoZin3-AM staining and increased zinc concentrations stained with Zinpyr-1. Furthermore, zinc supplementation after induced zinc deficiency leads to a fast and excessive rise of the intracellular free zinc levels in most cellular compartments.

Our study emphasizes the importance of zinc homeostasis and zinc distribution during cellular priming and for certain signaling cascades especially in T and B cells. Moreover, we demonstrated that zinc re-supplementation of zinc deficient cells results in significantly elevated intracellular free zinc concentrations compared to untreated controls. Hence, this underlines the need of a balanced zinc homeostasis for proper immune cell function.