Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli
Abstract Metal workers have an increased risk of severe lobar pneumonia due to exposure to metal fume particles, which lead to recent pneumococcal vaccination recommendations. To investigate the effects of metal fume‐derived zinc oxide (ZnO) and copper oxide (CuO) particles on airway immune response...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Global Challenges |
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| Online Access: | https://doi.org/10.1002/gch2.202400302 |
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| author | Jan Steffens Sabrina Michael Katharina Kuth Henner Hollert Miriam Du Marchie Sarvaas Andrijana Nesic Thomas Kraus Ralf Baumann |
| author_facet | Jan Steffens Sabrina Michael Katharina Kuth Henner Hollert Miriam Du Marchie Sarvaas Andrijana Nesic Thomas Kraus Ralf Baumann |
| author_sort | Jan Steffens |
| collection | DOAJ |
| description | Abstract Metal workers have an increased risk of severe lobar pneumonia due to exposure to metal fume particles, which lead to recent pneumococcal vaccination recommendations. To investigate the effects of metal fume‐derived zinc oxide (ZnO) and copper oxide (CuO) particles on airway immune responses, human THP‐1‐derived macrophages are exposed in vitro to the bacterial pathogen‐associated molecular patterns (PAMPs) lipopolysaccharide (LPS), lipoteichoic Acid (LTA), or peptidoglycan (PGN), together with particle suspensions. Particles are generated through metal inert gas (MIG) soldering. Spectrometric and microscopic analysis confirms CuO and ZnO as main components. Macrophage IL‐6 and TNF mRNAs are quantified by qPCR and secreted protein levels by electrochemiluminescent multi‐spot assay. A dose‐dependent increase in macrophage TNF and IL‐6 mRNA (4 h) and protein (24 h) levels following exposure to PAMPs is significantly inhibited by 2 µg mL−1 CuO/ZnO particles (n = 5). Additionally, CuO/ZnO particles significantly inhibit TNF protein expression in unstimulated macrophages, while IL‐6 protein levels are unaffected (n = 5). The presented in vitro immunotoxicity approach may extend existing new approach methodology (NAM) elements for chemical risk assessment and possibly exposure limit evaluation refinements. These findings implicate that CuO/ZnO particles suppress macrophage proinflammatory responses to PAMPs, potentially compromising lung immunity, underlining current vaccine recommendations and efforts for preventive occupational health guidelines. |
| format | Article |
| id | doaj-art-187106db20ed488cabcb9e8bfcfc6533 |
| institution | OA Journals |
| issn | 2056-6646 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | Global Challenges |
| spelling | doaj-art-187106db20ed488cabcb9e8bfcfc65332025-08-20T01:51:13ZengWileyGlobal Challenges2056-66462025-05-0195n/an/a10.1002/gch2.202400302Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial StimuliJan Steffens0Sabrina Michael1Katharina Kuth2Henner Hollert3Miriam Du Marchie Sarvaas4Andrijana Nesic5Thomas Kraus6Ralf Baumann7Institute for Translational Medicine (ITM) Medical School Hamburg (MSH) 20457 Hamburg GermanyInstitute for Occupational, Social and Environmental Medicine Medical Faculty University Hospital RWTH Aachen University 52074 Aachen GermanyInstitute for Occupational, Social and Environmental Medicine Medical Faculty University Hospital RWTH Aachen University 52074 Aachen GermanyDepartment Evolutionary Ecology and Environmental Toxicology Institute of Ecology, Evolution and Diversity Faculty Biological Sciences Goethe University Frankfurt 60438 Frankfurt GermanyInstitute for Occupational, Social and Environmental Medicine Medical Faculty University Hospital RWTH Aachen University 52074 Aachen GermanyInstitute for Translational Medicine (ITM) Medical School Hamburg (MSH) 20457 Hamburg GermanyInstitute for Occupational, Social and Environmental Medicine Medical Faculty University Hospital RWTH Aachen University 52074 Aachen GermanyInstitute for Translational Medicine (ITM) Medical School Hamburg (MSH) 20457 Hamburg GermanyAbstract Metal workers have an increased risk of severe lobar pneumonia due to exposure to metal fume particles, which lead to recent pneumococcal vaccination recommendations. To investigate the effects of metal fume‐derived zinc oxide (ZnO) and copper oxide (CuO) particles on airway immune responses, human THP‐1‐derived macrophages are exposed in vitro to the bacterial pathogen‐associated molecular patterns (PAMPs) lipopolysaccharide (LPS), lipoteichoic Acid (LTA), or peptidoglycan (PGN), together with particle suspensions. Particles are generated through metal inert gas (MIG) soldering. Spectrometric and microscopic analysis confirms CuO and ZnO as main components. Macrophage IL‐6 and TNF mRNAs are quantified by qPCR and secreted protein levels by electrochemiluminescent multi‐spot assay. A dose‐dependent increase in macrophage TNF and IL‐6 mRNA (4 h) and protein (24 h) levels following exposure to PAMPs is significantly inhibited by 2 µg mL−1 CuO/ZnO particles (n = 5). Additionally, CuO/ZnO particles significantly inhibit TNF protein expression in unstimulated macrophages, while IL‐6 protein levels are unaffected (n = 5). The presented in vitro immunotoxicity approach may extend existing new approach methodology (NAM) elements for chemical risk assessment and possibly exposure limit evaluation refinements. These findings implicate that CuO/ZnO particles suppress macrophage proinflammatory responses to PAMPs, potentially compromising lung immunity, underlining current vaccine recommendations and efforts for preventive occupational health guidelines.https://doi.org/10.1002/gch2.202400302CuO/ZnO particlesimmunosuppressive effects on macrophagesmetal (nano)‐particle exposurewelding and metal fumesworkplace safety and new approach methodologies (NAM) |
| spellingShingle | Jan Steffens Sabrina Michael Katharina Kuth Henner Hollert Miriam Du Marchie Sarvaas Andrijana Nesic Thomas Kraus Ralf Baumann Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli Global Challenges CuO/ZnO particles immunosuppressive effects on macrophages metal (nano)‐particle exposure welding and metal fumes workplace safety and new approach methodologies (NAM) |
| title | Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli |
| title_full | Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli |
| title_fullStr | Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli |
| title_full_unstemmed | Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli |
| title_short | Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli |
| title_sort | occupationally relevant zinc and copper containing metal fumes inhibit human thp 1 macrophage tnf and il 6 responses to bacterial stimuli |
| topic | CuO/ZnO particles immunosuppressive effects on macrophages metal (nano)‐particle exposure welding and metal fumes workplace safety and new approach methodologies (NAM) |
| url | https://doi.org/10.1002/gch2.202400302 |
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