Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung
Autor: | C. Albrecht, Thomas A. J. Kuhlbusch, D. van Berlo, Aalt Bast, Maja Hullmann, Agnes W. Boots, R. Schins, Verena Wilhelmi |
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Přispěvatelé: | GezondheidsRisico Analyse en Toxicologie, Farmacologie en Toxicologie, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: NUTRIM - R4 - Gene-environment interaction, RS: CARIM - R3 - Vascular biology |
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Pathology
Macrophage Health Toxicology and Mutagenesis Multi-walled carbon nanotubes Apoptosis Toxicology PULMONARY Fibrosis PLEURAL INFLAMMATION Lung Cell Line Transformed GENE-EXPRESSION Chemistry MESOTHELIAL CELLS RAW 264.7 MACROPHAGES CROCIDOLITE ASBESTOS FIBERS General Medicine Specific Pathogen-Free Organisms medicine.anatomical_structure Female medicine.symptom HEME OXYGENASE-1 medicine.medical_specialty NONFIBROUS PARTICLES Chemie Inflammation Caspase 3 Respiratory Mucosa Administration Inhalation medicine Animals Particle Size Nanotubes Carbon Macrophages Monocyte Hydrogen Peroxide Pneumonia IN-VITRO Macrophage Activation medicine.disease Molecular biology Mice Inbred C57BL Cell culture INTRATRACHEAL INSTILLATION Microscopy Electron Scanning Particulate Matter Reactive Oxygen Species Biomarkers |
Zdroj: | Archives of Toxicology, 88(9), 1725-1737. Springer |
ISSN: | 0340-5761 |
Popis: | There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard. |
Databáze: | OpenAIRE |
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