title: Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Inserm U955, Equipe 4, Créteil 94000, France. jorge.boczkowski@inserm.fr
authors: Agnès
authors: A
authors: Roulet
authors: Lucie
authors: L
authors: Armand
authors: Maylis
authors: M
authors: Dagouassat
authors: Françoise
authors: F
authors: Rogerieux
authors: Angélique
authors: A
authors: Simon-Deckers
authors: Esther
authors: E
authors: Belade
authors: Jeanne Tran
authors: JT
authors: Van Nhieu
authors: Sophie
authors: S
authors: Lanone
authors: Jean-Claude
authors: JC
authors: Pairon
authors: Ghislaine
authors: G
authors: Lacroix
authors: Jorge
authors: J
authors: Boczkowski
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D051547:Heme Oxygenase-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007442:Intubation, Intratracheal; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D023421:Models, Animal; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D010196:Pancreatic Elastase / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053260:Soot / Q000008:administration & dosage / Q000009:adverse effects*; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D053583:Interleukin-1beta; D053260:Soot; C009495:titanium dioxide; D014025:Titanium; D051547:Heme Oxygenase-1; D010196:Pancreatic Elastase; D053508:Matrix Metalloproteinase 12