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Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse

  • Organ Toxicity and Mechanisms
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Abstract

In the present work, we elaborated a synthetic lung surfactant composed of dipalmitoyl phosphatidylcholine (DPPC), phosphatidylglycerol, cholesterol and bovine serum albumin (BSA), as a vehicle to study the lung toxicity of pristine multi-walled carbon nanotubes (MWCNT). MWCNT were dispersed in surfactant, saline or saline containing DPPC, BSA, Pluronic® F68 or sodium dodecyl sulfate, for comparison. Dispersions were characterized visually, and by light microscopy, dynamic light scattering and transmission electronic microscopy (TEM). Deposition of surfactant-dispersed MWCNT in the lung of BALB/c mice upon single or repeated administrations was analyzed by histology and TEM. Inflammation and airway remodeling were assessed in bronchoalveolar lavage fluid (BALF) or lung tissue of mice by counting cells and quantifying cytokines, tumor growth factor (TGF)-β1 and collagen, and by histology. We found that the elaborated surfactant is more effective in dispersing MWCNT when compared to the other agents, while being biocompatible. Surfactant-dispersed MWCNT distributed all throughout the mouse airways upon single and repeated administrations and were observed in alveolar macrophages and epithelial cells, and in infiltrated neutrophils. Mice that received a single administration of MWCNT showed neutrophil infiltrate and greater concentrations of tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC) and interleukin (IL)-17 in BALF when compared to controls. After repeated MWCNT administrations, increases in macrophage number, KC and TGF-β1 levels in BALF, and collagen deposition and mucus hyperplasia in lung tissue were observed. Altogether, the elaborated lung surfactant could be a valuable tool to further study the toxicological impact of pristine MWCNT in laboratory animals.

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Acknowledgments

This work was supported by the Agence Nationale de la Recherche (ANR-08-CESA-017), the Centre National de la Recherche Scientifique, the Université de Strasbourg and the Réseau Alsace de Laboratoires en Ingénierie et Sciences pour l’Environnement. Carole Ronzani is the recipient of a PhD grant from the Ministère de l’Education Nationale, de la Recherche et de la Technologie. The authors thank the laboratory of the Unité de Pneumologie, d’Allergologie et de Pathologie respiratoire de l’environnement at the Hôpitaux Universitaires de Strasbourg, for endotoxin assays. They are also grateful to Pascal Kessler, Yves Lutz and Yannick Schwab (IGBMC) for fruitful discussions and suggestions.

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  1. Faculté de Pharmacie, Laboratoire de Conception et Application de Molécules Bioactives, CNRS, Université de Strasbourg, 74 route du Rhin, BP 60024, 67401, Illkirch Cedex, France

    Carole Ronzani, Luc Lebeau & Françoise Pons

  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre d’Imagerie, 1 rue Laurent Fries, 67400, Illkirch, France

    Coralie Spiegelhalter & Jean-Luc Vonesch

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  1. Carole Ronzani
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  2. Coralie Spiegelhalter
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Correspondence to Françoise Pons.

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Ronzani, C., Spiegelhalter, C., Vonesch, JL. et al. Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse. Arch Toxicol 86, 137–149 (2012). https://doi.org/10.1007/s00204-011-0741-y

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