Lung exposure to nanoparticles modulates an asthmatic response in a mouse model.
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.
Research Unit for Lung Toxicology, Dept of Occupational, Environmental and Insurance Medicine, KU Leuven, Leuven, Belgium.
S
S
Hussain
J A J
JA
Vanoirbeek
K
K
Luyts
V
V
De Vooght
E
E
Verbeken
L C J
LC
Thomassen
J A
JA
Martens
D
D
Dinsdale
S
S
Boland
F
F
Marano
B
B
Nemery
P H M
PH
Hoet
D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004804:Eosinophils; D006046:Gold / Q000009:adverse effects*; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000503:physiopathology*; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000009:adverse effects*; D009504:Neutrophils; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology; D014025:Titanium / Q000009:adverse effects*; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
C009495:titanium dioxide; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; D006046:Gold; D014025:Titanium