Lung exposure to nanoparticles modulates an asthmatic response in a mouse model

Eur Respir J. 2011 Feb;37(2):299-309. doi: 10.1183/09031936.00168509. Epub 2010 Jun 7.


The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO₂) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma. On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone-olive oil (AOO) on the dorsum of both ears (20 μL). On day 14, the mice were oropharyngeally dosed with 40 μL of a NP suspension (0.4 mg·mL⁻¹ (∼0.8 mg·kg⁻¹) TiO₂ or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 μL). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed. NP exposure in sensitised mice led to a two- (TiO₂) or three-fold (Au) increase in AHR, and a three- (TiO₂) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation. In conclusion, these results show that a low, intrapulmonary doses of TiO₂ or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / chemically induced*
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal
  • Eosinophils
  • Gold / adverse effects*
  • Immunoglobulin E / blood
  • Lung / physiopathology*
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / adverse effects*
  • Neutrophils
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / physiopathology
  • Titanium / adverse effects*
  • Toluene 2,4-Diisocyanate / toxicity*


  • titanium dioxide
  • Toluene 2,4-Diisocyanate
  • Immunoglobulin E
  • Gold
  • Titanium