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ABSTRACT
Background: Nanoparticles are increasingly suspected as a strong etiologic factor of granuloma formation. Aim of the Study: The aim of our study was to compare lung inflammatory response and histology changes following exposure of mice to two widely used nanoparticles: carbon nanotubes (MWCNT) and cadmium-based nanoparticles (QDOT705) in an attempt to better our understanding of granulomatous inflammation. Materials and Methods: Various groups of mice were included: control mice and mice that were intranasally instilled with QDOT or MWCNT. At defined time points post-challenge, bronchoalveolar lavages (BALs) and lung tissues were collected to study inflammatory and histologic changes. Results: Analyses of lung BAL fluids and tissues of nanoparticles-challenged mice in comparison to controls found: (1) increased cellularity in BALs, (2) increase of total protein concentration, LDH activity and proteolytic activity in BALs; (3) patchy granulomas, (4) macrophages, CD3 ± T, Treg and B cell infiltration in granulomatous areas; and (5) altered regulation of key inflammatory mediators and receptors. Importantly, these changes were nanoparticle type-dependent. Conclusion: Our work enhances understanding of nanoparticles-induced lung inflammatory and histological changes that result in granuloma formation. We provide compelling evidence that not only exposure to nanoparticles leads to granulomatous lung inflammation, but the severity of this latter is nanostructure type-dependent. Of importance, while nanotechnology has the potential to revolutionize various fields including medicine, nanoparticles form the potential for an entirely new lung health risk that it is necessary to take seriously into consideration by setting up and/or reinforcing adequate safety measures.
Acknowledgments
Authors would like to thank Hervé Farine and Julie Deverchere who contributed to ELISA, and Gelatin zymography and LDH activity assay analyses, respectively.
Declaration of interest
The authors report no conflicts of interest.
Ethical approval
All procedures were performed under protocols approved by the ethical committee «Comité d'Evaluation Commun au Centre Léon Bérard, à l'Animalerie de transit de l'ENS, au PBES et au laboratoire P4» (CECCAPP) of our institute (France, CECCAPP-LS-2014-002).
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Notes on contributors
Yves Pacheco
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Marine Ponchon
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Serge Lebecque
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Alain Calender
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Jean François Bernaudin
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Dominique Valeyre
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Marc Iglarz
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Daniel S. Strasser
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Rolf Studer
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Diego Freti
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Toufiq Renno
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB
Abederrazzaq Bentaher
Conception and design: YP, SL, TR, AB; Analysis and interpretation: MP, YP, MI, DS, RS, DF, FB AB; Drafting the manuscript for important intellectual content: YP, AC, MI, FB, DV, AB