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 Medicin...

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Autores principales:	Wolf-Grosse S, Rokstad AM, Ali S, Lambris JD, Mollnes TE, Nilsen AM, Stenvik J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e52
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spelling	oai:doaj.org-article:ff72f1f7e9324c6cbfe2dfc65d830e522021-12-02T02:21:11ZIron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model1178-2013https://doaj.org/article/ff72f1f7e9324c6cbfe2dfc65d830e522017-05-01T00:00:00Zhttps://www.dovepress.com/iron-oxide-nanoparticles-induce-cytokine-secretion-in-a-complement-dep-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Susann 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 further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood. Keywords: iron oxide nanoparticles, human whole blood, complement activation, cytokines, reactive oxygen species, complement inhibitorsWolf-Grosse SRokstad AMAli SLambris JDMollnes TENilsen AMStenvik JDove Medical PressarticleIron oxide nanoparticleshuman whole bloodcomplement activationcytokinesreactive oxygen speciesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3927-3940 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Iron oxide nanoparticles human whole blood complement activation cytokines reactive oxygen species Medicine (General) R5-920
spellingShingle	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
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 further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood. Keywords: iron oxide nanoparticles, human whole blood, complement activation, cytokines, reactive oxygen species, complement inhibitors
format	article
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
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Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

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