An in vitro coculture system for the detection of sensitization following aerosol exposure

Abstract

The aim of the study was to develop an in vitro model that mimics the alveolar-capillary barrier and that allows assessment of the respiratory sensitizing potential of substances. The 3D in vitro model cultured at the air liquid interface consists of alveolar type II epithelial cells (A549), endothelial cells (EA.hy926), macrophage-like cells (PMA-differentiated THP-1), and dendritic-like cells (non-differentiated THP-1). This alveolar model was exposed apically to nebulized chemical respiratory sensitizers (phthalic anhydride (PA) and trimellitic anhydride (TMA)) or to irritants (methyl salicylate (MeSa) and acrolein (Acr)) at concentrations inducing 25% cytotoxicity. The exposure to respiratory sensitizers induced dendritic-like cell activation and a specific cytokine release pattern, while exposure to irritants did not. In addition, the cell surface marker OX40L was found to identify dendritic-like cell activation by high molecular weight allergens. With this in vitro model we can postulate a set of promising markers that allow the discrimination of chemical respiratory sensitizers from irritants.