Open Access Research article

Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats

Agnès Roulet12, Lucie Armand12, Maylis Dagouassat12, Françoise Rogerieux3, Angélique Simon-Deckers12, Esther Belade12, Jeanne Tran Van Nhieu24, Sophie Lanone125, Jean-Claude Pairon125, Ghislaine Lacroix3 and Jorge Boczkowski1256*

Author Affiliations

1 Inserm U955, Equipe 4, Créteil 94000, France

2 Université Paris Est, Faculté de Médecine, Créteil 94000, France

3 Institut National de l’Environnement Industriel et des Risques (INERIS), Verneuil en Halatte, France

4 AP-HP, Hôpital Henri Mondor, Département de pathologie, Créteil, 94010, France

5 Centre Hospitalier Intercommunal, Service de pneumologie et pathologie professionnelle, Créteil, 94000, France

6 AP-HP, Hôpital Henri Mondor, Service de Physiologie Explorations Fonctionnelles, Créteil, 94000, France

For all author emails, please log on.

BMC Pulmonary Medicine 2012, 12:38  doi:10.1186/1471-2466-12-38

Published: 31 July 2012



Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms.


On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry.


TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema.


TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages.

COPD; Occupational medicine; Particles; Toxicity