Proteomic analysis of bronchoalveolar lavage fluid in rat exposed to TiO nanostructured aerosol by inhalation.
Fiche publication
Date publication
septembre 2019
Journal
Journal of proteomics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RIHN Bertrand
Tous les auteurs :
Chézeau L, Kohlstaedt LA, Le Faou A, Cosnier F, Rihn B, Gaté L
Lien Pubmed
Résumé
The pulmonary toxicological properties of inhaled titanium dioxide were studied using bronchoalveolar lavage fluid (BALF) cytology and proteomics analyses. Fischer 344 rats were exposed to 10 mg/m of TiO nanostructured aerosol by nose-only inhalation for 6 h/day, 5 days/week for 4 weeks. Lung samples were collected up to 180 post-exposure days. As previously described, cytological analyses of BALF showed a strong inflammatory response up to 3 post-exposure days, which persisted however, at a lower intensity up to 180 days. In addition, using Multidimensional Protein Identification Technology (MudPIT), we identified a total of 107, 50 and 45 proteins (UniprotKB identifiers) differentially expressed in exposed rats immediately, 3 and 180 days after the end of exposure respectively. Increased levels of inflammatory proteins, members of proteasome, various histones, proteins involved in cytoskeleton organization, were noticed up to 3 days (short-term response). Some of these proteins were linked with Neutrophil Extracellular Trap formation (NETosis). Long-term response was also characterized by a persistent altered expression of proteins up to 180 days. Altogether, these results suggest that exposure to low toxicity low solubility nanomaterials such as TiO may induce long-term changes in the pulmonary protein expression pattern of which the physio-pathological consequences are unknown. SIGNIFICANCE: This paper describes in rats, at the pulmonary level, the effects of inhaled nanostructured aerosol of TiO on the secreted proteins found in the broncho-alveolar space by comparing the proteomic profile in broncho-alveolar lavage fluid supernatants of control and exposed animals. This work brings new insights about the early events occurring following the end of exposure and suggests the formation of Neutrophil Extracellular Traps (NETosis) that could be interpret as a potential early mechanism of defense against TiO nanoparticles. This work also describes the long term effects (180 post-exposure days) of such an exposure and the change in secreted protein expression in the absence of significant histopathological modifications.
Mots clés
Long-term response, Lung inflammation, NETosis, Protein expression profile, Short-term response, Titanium dioxide
Référence
J Proteomics. 2019 09 15;207:103451