Advanced in vitro exposure systems.

In vitro model for the prediction of respiratory sensitization of inhaled chemicals and protein allergens.

11. Mar. 2018

User Group Meeting 2018

Chary A.1,2, Serchi T.1, Cambier S.1, Moschini E.1, Contal S.1, Hennen J.2, Ezendam J.3, Blömeke B.2, Gutleb A.C.1
1 Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology (LIST), Luxembourg.
2 Department of Environmental Toxicology, Trier University, Germany. 3Centre for Environmental Protection,National Institute for Public Health and the Environment (RIVM), The Netherlands.

Aim
- Adapt a 3D-coculture system previously developed by us (Klein et al. 2013) allowing the study of respiratory sensitization processes by including dendritic cells, which have a crucial role in sensitization
- Find markers for the assessment of the respiratory sensitizing potential of inhaled compounds by measuring the activation of DCs as well as the release of cytokines

 

Introduction
- Chemical respiratory sensitization resulting from occupational exposure to synthetic compounds has increased over the last decades leading to important occupational health issues.
- Complex in vitro co-culture systems represent valuable tools to understand the mechanisms involved in lung sensitization.
- No validated in vitro model is currently available to assess the respiratory sensitization potential of chemicals.
- An interesting in vitro model developed by Klein et al. in 2013 combining alveolar type II epithelial cell line A549, acute monocyte cell line THP-1 cells differentiated into macrophage like cells, endothelial cells EA.hy 926 and human mast cell line HMC-1 in coculture has been developed to assess the toxic effects of particles at the alveolar barrier. The coculture was designed in a 3D-organisation to mimic at best the in vivo histology of the alveolar barrier and cultured at the air liquid interface (ALI) to mimic realistic exposure of inhaled compounds.
- DCs, which have a crucial role in sensitization, need indeed to be included in such model to study the relevant process of sensitization. The coculture was redesigned to address the sensitizing potential of inhaled compounds in a relevant way, including the possibility of migration of DCs to ensure to have a functional model.

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