The effects of fine particulate matter (SRM 2786) on three different 3D lung models exposed at the air-liquid interface – A comparative study

• DOI: 10.1016/j.tiv.2024.105841
• Publication Date: 2024-05-08T16:25:11Z
• Authors: Vegard Sæter Gryt...; Tonje Skuland; Jarle Ballangby; Magne Refsnes; Marit Låg; Johan Øvrevik; Espen Mariussen
• Keywords: Air Pollutants; Mucus; Macrophages; Cell Culture Techniques; Humans; Cytokines; Particulate Matter; Epithelial Cells; Lung; Coculture Techniques; Cell Line

3D cell culture models exposed at the air-liquid interface (ALI) represent a potential alternative to animal experiments for hazard and risk assessment of inhaled compounds. This study compares cocultures composed of either Calu-3, A549 or HBEC3-KT lung epithelial cells, cultured together with THP-1-derived macrophages and EA.hy926 endothelial cells, in terms of barrier capacity and responses to a standard reference sample of fine particulate matter (SRM 2786). High-content imaging analysis revealed a similar cellular composition between the different cell models. The 3D cell cultures with Calu-3 cells showed the greatest barrier capacity, as measured by transepithelial electrical resistance and permeability to Na-fluorescein. Mucus production was detected in 3D cell cultures based on Calu-3 and A549 cells. Exposure to SRM 2786 at ALI increased cytokine release and expression of genes associated with inflammation and xenobiotic metabolism. Moreover, the presence of THP-1-derived macrophages was central to the cytokine responses in all cell models. While the different 3D cell culture models produced qualitatively similar responses, more pronounced pro-inflammatory responses were observed in the basolateral compartment of the A549 and HBEC3-KT models compared to the Calu-3 model, likely due to their reduced barrier capacity and lower retention of secreted mediators in the apical compartment.