| dc.description.abstract | Particulate matter (PM) with an aerodynamic diameter below 2.5 µm (PM2.5) has been identified as the main contributor to the adverse health effects associated with air pollution. However, current regulations might not allow for accurate assessment of the smallest fractions of PM2.5. These fractions, called ultrafine particles (UFP), have a massive surface area and an ability to penetrate deep into the airways and translocate into circulation. This has contributed to the concept of the “Trojan Horse effect”, which suggests that UFPs derived from combustion serve as carriers for organic contaminants, enabling them access to otherwise unreachable tissues and organs. Thus, the present study aimed investigate how the organic fraction of such particles contribute to biological effects associated with UFP exposure. To achieve this, cell models representing the human respiratory system were exposed to carbon black nanoparticles, either pristine or coated with organic compounds, and relevant biomarkers for cytotoxicity, pro-inflammatory responses, and xenobiotic metabolism were used to assess and compare effects. Printex 90 (P90) was used as a model for the carbon core of ultrafine combustion particles and Benzo[a]pyrene (B[a]P) and Pyrene (Pyr) as models for the organic compounds surrounding the core. Two different 3D lung models were employed and exposed at the air-liquid interface (ALI) to simulate the bronchial and alveolar epithelium, as well as the blood-air barrier at the respiratory bronchioles and alveolar-capillary barrier. Calu-3 bronchial epithelial cells or A549 alveolar epithelial cells were grown together with THP-1 derived macrophages in the apical compartment, while vascular endothelial cells Ea.Hy926 cells were grown in the basolateral compartment. The same cell lines were also subjected for monoculture experiments. Significant differences between P90 and P90+PAH were observed in Ea.Hy monocultures, with P90+PAH inducing an overall weaker response compared to P90 alone. In 3D cultures, B[a]P significantly increased both epithelial and endothelial CYP1A1 expression. Conversely, P90+B[a]P did not affect CYP1A1 expression. The inability to induce CYP1A1 may indicate that B[a]P was not readily bioavailable when particle-bound, and did not translocate across the epithelial barrier. Furthermore, the reduced effects of PAH-coated particles relative to uncoated particles suggest that P90s toxic potential was decreased when PAH was present. These findings indicate that the chemical properties of P90+B[a]P did not allow for B[a]P release, but instead mitigated P90 toxicity, possibly by reducing its specific surface area. | eng |