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Zinc induced apoptotic death of mouse dendritic cells

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Abstract

Zinc ions (Zn2+) are food components with favourable effects in infectious disease. Zn2+ is taken up into dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. In other cell types, Zn2+ has been shown to stimulate the formation of ceramide, which is in turn known to trigger suicidal cell death. The present study explored whether Zn2+ modifies ceramide formation and survival of bone marrow derived DCs. To this end, DCs were isolated from acid sphingomyelinase knockout (asm −/−) and corresponding wild type (asm +/+) mice and treated with different concentrations of Zn2+. Ceramide formation was assessed with anti-ceramide antibodies in FACS and immunohistochemical analysis, sub-G1 cell population by FACS analysis, break down of phosphatidylserine asymmetry by annexin V binding, cell death by propidium iodide incorporation, metabolic cell activity by MTT assay, ROS production from dichlorofluorescein fluorescence and activation of MAPKs by Western blotting. The treatment of asm +/+ DCs with low Zn2+ concentrations (up to 100 μM) was followed by ceramide formation, increase in sub-G1 cell population and phosphatidylserine exposure, effects blunted in asm −/− DCs. The treatment of DCs with C2-ceramide increased the percentage of sub-G1 and apoptotic DCs from both genotypes. Zn2+ led to similar activation of MAPKs in asm +/+ and asm −/− DCs and did not affect ROS production. Higher concentrations of Zn2+ led to a marked increase of propidium iodide incorporation in DCs of both genotypes. The present study reveals that in DCs Zn2+ triggers ceramide formation, which in turn compromises cell survival.

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Acknowledgments

The authors gratefully acknowledge the meticulous preparation of the manuscript by Lejla Subasic and Tanja Loch. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 766).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Ekaterina Shumilina, Nguyen Thi Xuan, Evi Schmid, Shefalee K. Bhavsar, Kalina Szteyn, Shuchen Gu & Florian Lang

  2. Department of Microbial Genetics, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Friedrich Götz

  3. Physiologisches Institut der Universität Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Florian Lang

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  1. Ekaterina Shumilina
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  2. Nguyen Thi Xuan
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Correspondence to Florian Lang.

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Shumilina, E., Xuan, N.T., Schmid, E. et al. Zinc induced apoptotic death of mouse dendritic cells. Apoptosis 15, 1177–1186 (2010). https://doi.org/10.1007/s10495-010-0520-x

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