Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model
Susann Wolf-Grosse,1 Anne Mari Rokstad,1–3 Syed Ali,4 John D Lambris,5 Tom E Mollnes,2,6–9 Asbjørn M Nilsen,1,* Jørgen Stenvik1,2,* 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, Norwegian University...
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ftdoajarticles:oai:doaj.org/article:ff72f1f7e9324c6cbfe2dfc65d830e52 2023-05-15T15:45:26+02:00 Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model Wolf-Grosse S Rokstad AM Ali S Lambris JD Mollnes TE Nilsen AM Stenvik J 2017-05-01T00:00:00Z https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e52 EN eng Dove Medical Press https://www.dovepress.com/iron-oxide-nanoparticles-induce-cytokine-secretion-in-a-complement-dep-peer-reviewed-article-IJN https://doaj.org/toc/1178-2013 1178-2013 https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e52 International Journal of Nanomedicine, Vol Volume 12, Pp 3927-3940 (2017) Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920 article 2017 ftdoajarticles 2022-12-31T08:04:51Z Susann Wolf-Grosse,1 Anne Mari Rokstad,1–3 Syed Ali,4 John D Lambris,5 Tom E Mollnes,2,6–9 Asbjørn M Nilsen,1,* Jørgen Stenvik1,2,* 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 3Central Norway Regional Health Authority, Stjørdal, Norway; 4Division of Neurotoxicology, US FDA/National Center for Toxicological Research, Jefferson, AR, 5Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, 7Research Laboratory, Nordland Hospital, Bodø, 8K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, 9Faculty of Health Sciences, K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway *These authors contributed equally to this work Abstract: Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which ... Article in Journal/Newspaper Bodø Bodø Nordland Nordland Nordland University of Tromsø Directory of Open Access Journals: DOAJ Articles Bodø ENVELOPE(14.405,14.405,67.280,67.280) Jebsen ENVELOPE(-45.683,-45.683,-60.717,-60.717) Mollnes ENVELOPE(19.361,19.361,70.084,70.084) Norway Tromsø |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920 |
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Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920 Wolf-Grosse S Rokstad AM Ali S Lambris JD Mollnes TE Nilsen AM Stenvik J Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
topic_facet |
Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920 |
description |
Susann Wolf-Grosse,1 Anne Mari Rokstad,1–3 Syed Ali,4 John D Lambris,5 Tom E Mollnes,2,6–9 Asbjørn M Nilsen,1,* Jørgen Stenvik1,2,* 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 3Central Norway Regional Health Authority, Stjørdal, Norway; 4Division of Neurotoxicology, US FDA/National Center for Toxicological Research, Jefferson, AR, 5Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, 7Research Laboratory, Nordland Hospital, Bodø, 8K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, 9Faculty of Health Sciences, K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway *These authors contributed equally to this work Abstract: Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which ... |
format |
Article in Journal/Newspaper |
author |
Wolf-Grosse S Rokstad AM Ali S Lambris JD Mollnes TE Nilsen AM Stenvik J |
author_facet |
Wolf-Grosse S Rokstad AM Ali S Lambris JD Mollnes TE Nilsen AM Stenvik J |
author_sort |
Wolf-Grosse S |
title |
Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
title_short |
Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
title_full |
Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
title_fullStr |
Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
title_full_unstemmed |
Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
title_sort |
iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model |
publisher |
Dove Medical Press |
publishDate |
2017 |
url |
https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e52 |
long_lat |
ENVELOPE(14.405,14.405,67.280,67.280) ENVELOPE(-45.683,-45.683,-60.717,-60.717) ENVELOPE(19.361,19.361,70.084,70.084) |
geographic |
Bodø Jebsen Mollnes Norway Tromsø |
geographic_facet |
Bodø Jebsen Mollnes Norway Tromsø |
genre |
Bodø Bodø Nordland Nordland Nordland University of Tromsø |
genre_facet |
Bodø Bodø Nordland Nordland Nordland University of Tromsø |
op_source |
International Journal of Nanomedicine, Vol Volume 12, Pp 3927-3940 (2017) |
op_relation |
https://www.dovepress.com/iron-oxide-nanoparticles-induce-cytokine-secretion-in-a-complement-dep-peer-reviewed-article-IJN https://doaj.org/toc/1178-2013 1178-2013 https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e52 |
_version_ |
1766379825216356352 |