Effects of different amosite preparations on macrophages, lung damages, and autoimmunity.
Autor: | Lescoat A; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France.; Department of Internal Medicine & Clinical Immunology, Rennes University Hospital, 35000, Rennes, France., Leinardi R; Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale Et Clinique (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 57, Bte B-1.57.06, 1200, Brussels, Belgium., Pouxvielh K; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France., Yakoub Y; Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale Et Clinique (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 57, Bte B-1.57.06, 1200, Brussels, Belgium., Lelong M; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France., Pochet A; Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale Et Clinique (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 57, Bte B-1.57.06, 1200, Brussels, Belgium., Dumontet E; CHU Rennes, Pôle de Biologie, Rennes, France., Bellamri N; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France., Le Tallec E; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France.; Department of Internal Medicine & Clinical Immunology, Rennes University Hospital, 35000, Rennes, France., Pavan C; 'G. Scansetti' Interdepartmental Center for Studies On Asbestos and Other Toxic Particulates, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy.; Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy., Turci F; 'G. Scansetti' Interdepartmental Center for Studies On Asbestos and Other Toxic Particulates, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy.; Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy., Paris C; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France.; Service de Santé Au Travail Et Pathologie Professionnelle, CHU Rennes, 35000, Rennes, France., Huaux F; Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale Et Clinique (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 57, Bte B-1.57.06, 1200, Brussels, Belgium., Lecureur V; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France. valerie.lecureur@univ-rennes.fr.; UMR-INSERM 1085, Campus Santé, 2 Avenue du Pr Léon Bernard, 35043, Rennes Cedex, France. valerie.lecureur@univ-rennes.fr. |
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Jazyk: | angličtina |
Zdroj: | Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2024 Feb; Vol. 102 (2), pp. 197-211. Date of Electronic Publication: 2023 Nov 28. |
DOI: | 10.1007/s00109-023-02401-9 |
Abstrakt: | The underlying mechanisms of asbestos-related autoimmunity are poorly understood. As the size, surface reactivity, and free radical activity of asbestos particles are considered crucial regarding the health effects, this study aims to compare the effects of exposure to pristine amosite (pAmo) or milled amosite (mAmo) particles on lung damage, autoimmunity, and macrophage phenotype. Four months after lung exposure to 0.1 mg of amosite, BAL levels of lactate dehydrogenase, protein, free DNA, CCL2, TGF-β1, TIMP-1, and immunoglobulin A of pAmo-exposed C57Bl/6 mice were increased when compared to fluids from control- and mAmo-exposed mice. Effects in pAmo-exposed mice were associated with lung fibrosis and autoimmunity including anti-double-strand DNA autoantibody production. mAmo or pAmo at 20 µg/cm 2 induced a pro-inflammatory phenotype characterized by a significant increase in TNFα and IL-6 secretion on human monocyte-derived macrophages (MDMs). mAmo and pAmo exposure induced a decrease in the efferocytosis capacities of MDMs, whereas macrophage abilities to phagocyte fluorescent beads were unchanged when compared to control MDMs. mAmo induced IL-6 secretion and reduced the percentage of MDMs expressing MHCII and CD86 markers involved in antigen and T-lymphocyte stimulation. By contrast, pAmo but not mAmo activated the NLRP3 inflammasome, as evaluated through quantification of caspase-1 activity and IL-1β secretion. Our results demonstrated that long-term exposure to pAmo may induce significant lung damage and autoimmune effects, probably through an alteration of macrophage phenotype, supporting in vivo the higher toxicity of entire amosite (pAmo) with respect to grinded amosite. However, considering their impact on efferocytosis and co-stimulation markers, mAmo effects should not be neglected. KEY MESSAGES: Lung fibrosis and autoimmunity induced by amosite particles depend on their physicochemical characteristics (size and surface) Inhalation exposure of mice to pristine amosite fibers is associated with lung fibrosis and autoimmunity Anti-dsDNA antibody is a marker of autoimmunity in mice exposed to pristine amosite fibers Activation of lung mucosa-associated lymphoid tissue, characterized by IgA production, after exposure to pristine amosite fibers Pristine and milled amosite particle exposure reduced the efferocytosis capacity of human-derived macrophages. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
Databáze: | MEDLINE |
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