A newly developed in vitro model of the human epithelial airway barrier to study the toxic potential of nanoparticles.
The potential health effects of inhaled engineered nanoparticles are almost unknown. To avoid and replace toxicity studies with animals, a triple cell co-culture system composed of epithelial cells, macrophages and dendritic cells was established, which simulates the most important barrier functions of the epithelial airway. Using this model, the toxic potential of titanium dioxide was assessed by measuring the production of reactive oxygen species and the release of tumour necrosis factor alpha. The intracellular localisation of titanium dioxide nanoparticles was analyzed by energy filtering transmission electron microscopy. Titanium dioxide nanoparticles were detected as single particles without membranes and in membrane-bound agglomerates. Cells incubated with titanium dioxide particles showed an elevated production of reactive oxygen species but no increase of the release of tumour necrosis factor alpha. Our in vitro model of the epithelial airway barrier offers a valuable tool to study the interaction of particles with lung cells at a nanostructural level and to investigate the toxic potential of nanoparticles.
Institute of Anatomy, Division of Histology, University of Bern, Bern, Switzerland. rothen@ana.unibe.ch
Barbara
B
Rothen-Rutishauser
Loretta
L
Mueller
Fabian
F
Blank
Christina
C
Brandenberger
Christian
C
Muehlfeld
Peter
P
Gehr
D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects*; D014025:Titanium
D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium