Effect of combustion particle morphology on biological responses in a Co-culture of human lung and macrophage cells

Atmospheric aging of combustion particles alters their chemical composition and morphology. Previous studies have reported differences in toxicological responses after exposure to fresh versus aged particles, with chemical composition being the prime suspect behind the differences. However, less is known about the contribution of morphological differences in atmospherically aged particles to toxicological responses, possibly due to the difficulty in resolving the two properties (composition and morphology) that change simultaneously. This study altered the shape of lab-generated combustion particles, without affecting the chemical composition, from fractal-like to a more compact spherical shape, using a water condensation-evaporation method. The two shapes were exposed to a co-culture of human airway epithelial (A549) and differentiated human monocyte (THP-1) cells at air-liquid interface (ALI) conditions. The particles with different shapes were deposited using an electrostatic field-based ALI chamber. For the same mass dose, both shapes were internalized by cells, induced a pro-inflammatory response (IL-8 and TNF alpha), and enhanced CYP1A1 gene expression compared to air controls. The more compact spherical particles (representative of atmospherically aged particles) induced more early apoptosis and release of TNF alpha compared to the more fractal-like particles. These results suggest a contribution of morphology to the increased toxicity of aged combustion-derived particles.