nn9b06860_si_001.pdf (4.29 MB)
Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multiwalled Carbon Nanotubes
journal contribution
posted on 2020-03-19, 20:30 authored by Hana Barosova, Anna G. Maione, Dedy Septiadi, Monita Sharma, Laetitia Haeni, Sandor Balog, Olivia O’Connell, George R. Jackson, David Brown, Amy J. Clippinger, Patrick Hayden, Alke Petri-Fink, Vicki Stone, Barbara Rothen-RutishauserExpansion in production
and commercial use of nanomaterials increases
the potential human exposure during the lifecycle of these materials
(production, use, and disposal). Inhalation is a primary route of
exposure to nanomaterials; therefore it is critical to assess their
potential respiratory hazard. Herein, we developed a three-dimensional
alveolar model (EpiAlveolar) consisting of human primary alveolar
epithelial cells, fibroblasts, and endothelial cells, with or without
macrophages for predicting long-term responses to aerosols. Following
thorough characterization of the model, proinflammatory and profibrotic
responses based on the adverse outcome pathway concept for lung fibrosis
were assessed upon repeated subchronic exposures (up to 21 days) to
two types of multiwalled carbon nanotubes (MWCNTs) and silica quartz
particles. We simulate occupational exposure doses for the MWCNTs
(1–30 μg/cm2) using an air–liquid interface
exposure device (VITROCELL Cloud) with repeated exposures over 3 weeks.
Specific key events leading to lung fibrosis, such as barrier integrity
and release of proinflammatory and profibrotic markers, show the responsiveness
of the model. Nanocyl induced, in general, a less pronounced reaction
than Mitsui-7, and the cultures with human monocyte-derived macrophages
(MDMs) showed the proinflammatory response at later time points than
those without MDMs. In conclusion, we present a robust alveolar model
to predict inflammatory and fibrotic responses upon exposure to MWCNTs.