Cellular and Molecular Toxicity of Atmospherically Aged Anthropogenic and Biogenic Aerosols in an Epithelial-Endothelial Coculture Using Adverse Outcome Pathways as Risk Assessment

SVENJA OFFER, Sebastiano Di Bucchianico, Hendryk Czech, Michal Pardo, Rasha Alsaleh, Christian Kersch, Simone Schmitz-Spanke, Yinon Rudich, Ralf Zimmermann, AeroHealth Team , Helmholtz Zentrum München

     Abstract Number: 310
     Working Group: Health-Related Aerosols

Abstract
Secondary organic aerosols (SOA) formed from anthropogenic and biogenic volatile precursors substantially contribute to the fine particulate matter (PM_2.5) burden, which has been associated with adverse human health effects. However, the molecular and cellular effects of atmospheric aging processes remain largely unknown. In this work, we aimed to elucidate the complexity of atmospheric aerosol toxicology by applying controlled model aerosols for realistic in vitro exposure at the air-liquid interface in a multicellular lung tissue model.

To achieve this goal, we generated aerosols by atmospheric aging of volatile biogenic (β-pinene) or anthropogenic (naphthalene) model precursors of SOA that condensed on soot particles. In-depth physicochemical characterization revealed similar physical properties and distinct chemical composition of generated SOA aerosols. The anthropogenic SOA was associated with the formation of more oxidized and more aromatic organic species with a higher oxidative potential and a greater extent of unsaturated carbonyls compared to biogenic derived SOA.

We discriminated the induced toxicological effects by exposing the multicellular model system, consisting of a lung epithelial cell line (A549) and an endothelial cell line (EA.hy926) in a 3D orientation. At a functional level, anthropogenic SOA largely augmented the secretion of the proinflammatory cytokine IL8 and the oxidative stress marker malondialdehyde compared to the biogenic SOA. Moreover, naphthalene-derived SOA significantly induced primary (A549) and secondary (EA.hy926) genotoxicity as well as the cross-activation of endothelial cells (angiogenic potential). Integrated transcriptomic and metabolomic analysis revealed an induction of stress-related airway remodeling in A549 cells and the involvement of pathways for intracellular signal transduction (PI3K/AKT) and endothelial dysfunction (iNOS; PDGF) in EA.hy926 cells, especially after exposure to the anthropogenic SOA. This mechanistic information was used to describe an adverse outcome pathway framework supporting a pivotal role of PM chemical composition in toxicological outcomes.