Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7991
Authors: Ponath, Viviane
Kaina, Bernd
Title: Death of monocytes through oxidative burst of macrophages and neutrophils : killing in trans
Online publication date: 13-Oct-2022
Year of first publication: 2017
Language: english
Abstract: Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to the pathogenesis of inflammatory diseases. Therefore, a mechanism maintaining a balance in the monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired in DNA repair, rendering them vulnerable to genotoxic stress while monocyte-derived macrophages are DNA repair competent and genotoxic stress-resistant. Based on these findings, we hypothesized that monocytes can be selectively killed by reactive oxygen species (ROS) produced by activated macrophages. We also wished to know whether monocytes and macrophages are protected against their own ROS produced following activation. To this end, we studied the effect of the ROS burst on DNA integrity, cell death and differentiation potential of monocytes. We show that monocytes, but not macrophages, stimulated for ROS production by phorbol-12-myristate-13-acetate (PMA) undergo apoptosis, despite similar levels of initial DNA damage. Following co-cultivation with ROS producing macrophages, monocytes displayed oxidative DNA damage, accumulating DNA single-strand breaks and a high incidence of apoptosis, reducing their ability to give rise to new macrophages. Killing of monocytes by activated macrophages, termed killing in trans, was abolished by ROS scavenging and was also observed in monocytes co-cultivated with ROS producing activated granulocytes. The data revealed that monocytes, which are impaired in the repair of oxidised DNA lesions, are vulnerable to their own ROS and ROS produced by macrophages and granulocytes and support the hypothesis that this is a mechanism regulating the amount of monocytes and macrophages in a ROS-enriched inflammatory environment.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7991
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use: https://creativecommons.org/licenses/by/4.0/
Journal: PLOS ONE
12
1
Pages or article number: e0170347
Publisher: PLOS
Publisher place: San Francisco, California, US
Issue date: 2017
ISSN: 1932-6203
Publisher URL: http://dx.doi.org/10.1371/journal.pone.0170347
Publisher DOI: 10.1371/journal.pone.0170347
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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