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Disulfiram Inhibits Opsonin-Independent Phagocytosis of In Vivo Activated Human In-Vivo Activated Macrophages and Dendritic Cells with Variable Effects on Mitochondrial Stress and Cell Death
Li, C.; Schneider, J.M.; Schneider, E.M. Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases. Cells2024, 13, 535.
Li, C.; Schneider, J.M.; Schneider, E.M. Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases. Cells 2024, 13, 535.
Li, C.; Schneider, J.M.; Schneider, E.M. Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases. Cells2024, 13, 535.
Li, C.; Schneider, J.M.; Schneider, E.M. Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases. Cells 2024, 13, 535.
Abstract
Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.
Keywords
in vivo activated macrophages; dendritic cells; software to monitor phagocytosis and migration; disulfiram; mitochondria; oxidative stress
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
