Intracellular zinc during cell activation and zinc deficiency

Benjamin Rolles; Martina Maywald; Lothar Rink

doi:10.1016/j.jtemb.2021.126864

Intracellular zinc during cell activation and zinc deficiency

J Trace Elem Med Biol. 2021 Dec:68:126864. doi: 10.1016/j.jtemb.2021.126864. Epub 2021 Sep 20.

Authors

Benjamin Rolles¹, Martina Maywald², Lothar Rink³

Affiliations

¹ Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Germany.
² Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany.
³ Institute of Immunology, Faculty of Medicine, RWTH Aachen University, University Hospital, Pauwelsstraße 30, 52074, Aachen, Germany. Electronic address: LRink@UKAachen.de.

PMID: 34562730
DOI: 10.1016/j.jtemb.2021.126864

Abstract

Introduction: 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.

Material and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: interleukin signaling; second messenger; zinc; zinc deficiency; zinc homeostasis.

MeSH terms

Chelating Agents
Ethylenediamines
Leukocytes, Mononuclear
T-Lymphocytes
Trace Elements*
Zinc* / deficiency

Substances

Chelating Agents
Ethylenediamines
Trace Elements
Zinc