(194a) Effect of Combustion Particle Morphology on Biological Responses in a Co-Culture of Human Lung Epithelial and Macrophage-like Cells

Background. Freshly generated combustion particles are hydrophobic and form fiber-like agglomerates with an average fractal dimension of 1.8. However, after aging in the atmosphere, particles become more hydrophilic allowing adsorption of water. When this water evaporates,it exerts capillary forces between the primary particles of the agglomerate, causing the structure to collapse and become more compact spheres-like. Previous studies with fresh and aged combustion particles have linked the changing chemical composition to be the prime suspect behind the observed differences in toxicological response. However, little is known about the contribution of morphological differences in atmospherically aged particles to their toxicological response, possibly due to the difficulty in resolving the two properties (composition and morphology) that change simultaneously. A method to change particle morphology without the need to change chemical composition would help elucidate the effect of this morphological change on cellular responses.

Methods. This study altered the shape of lab-generated combustion particles, without affecting the chemical composition, from fiber-like to a more compact spherical shape using a water condensation-evaporation method. Using an electrostatic field-based air-liquid exposure (ALI) chamber, the two shapes were exposed to a co-culture of human airway epithelial (A549) and differentiated human monocyte (THP-1) cells at ALI conditions.

Results. For the same mass dose of 2 mg/cm², both shapes were ingested by cells, and induced a pro-inflammatory response (IL-8 and TNFα) 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 TNFα compared to the more fiber-like particles.

Conclusions. The results suggest a contribution of morphology to the increased toxicity of aged particles.