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Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes

  • Inorganic Compounds
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Abstract

Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive. However, lower doses of some mercurials stimulate the immune system, inducing different forms of autoimmunity, autoantibodies, and glomerulonephritis in rodents. Furthermore, some studies suggest a connection between mercury exposure and the occurrence of autoantibodies against nuclear components and granulocyte cytoplasmic proteins in humans. Still, the underlying mechanisms need to be clarified. The present study investigates the formation of neutrophil extracellular traps (NETs) in response to thimerosal and its metabolites ethyl mercury (EtHg), thiosalicylic acid, and mercuric ions (Hg2+). Only EtHg and Hg2+ triggered NETosis. It was independent of PKC, ERK1/2, p38, and zinc signals and not affected by the NADPH oxidase inhibitor DPI. Instead, EtHg and Hg2+ triggered NADPH oxidase-independent production of ROS, which are likely to be involved in mercurial-induced NET formation. This finding might help understanding the autoimmune potential of mercurial compounds. Some diseases, to which a connection with mercurials has been shown, such as Wegener’s granulomatosis and systemic lupus erythematosus, are characterized by high prevalence of autoantibodies against neutrophil-specific auto-antigens. Externalization in the form of NETs may be a source for exposure to these self-antigens. In genetically susceptible individuals, this could be one step in the series of events leading to autoimmunity.

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Authors and Affiliations

  1. Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, 13355, Berlin, Germany

    Hajo Haase

  2. Medical Faculty, Institute of Immunology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany

    Hajo Haase, Silke Hebel, Gabriela Engelhardt & Lothar Rink

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  1. Hajo Haase
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  2. Silke Hebel
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  3. Gabriela Engelhardt
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  4. Lothar Rink
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Correspondence to Hajo Haase.

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Haase, H., Hebel, S., Engelhardt, G. et al. Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes. Arch Toxicol 90, 543–550 (2016). https://doi.org/10.1007/s00204-015-1484-y

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  • DOI: https://doi.org/10.1007/s00204-015-1484-y

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