https://doi.org/10.1186/s12989-024-00600-x
Svenja Offer1,2, Sebastiano Di Bucchianico1,2,3, Hendryk Czech1,2, Michal Pardo4, Jana Pantzke1,2, Christoph Bisig1, Eric Schneider2,3, Stefanie Bauer1, Elias J. Zimmermann1,2, Sebastian Oeder1, Elena Hartner1,2, Thomas Gröger1,2, Rasha Alsaleh5, Christian Kersch5, Till Ziehm6, Thorsten Hohaus6, Christopher P. Rüger2,3, Simone Schmitz-Spanke5, Jürgen Schnelle-Kreis1, Martin Sklorz1, Astrid Kiendler-Scharr6, Yinon Rudich4 and Ralf Zimmermann1,2,3
1Joint Mass Spectrometry Center (JMSC) at Comprehensive Molecular Analytics (CMA), Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
2Joint Mass Spectrometry Center (JMSC) at Analytical Chemistry, Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 27, D-18059 Rostock, Germany
3Department Life, Light & Matter (LLM), University of Rostock, D-18051 Rostock, Germany
4Department of Earth and Planetary Sciences, Faculty of Chemistry, Weizmann Institute of Science, 234 Herzl Street, POB 26, Rehovot ISR-7610001, Israel
5Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander University of Erlangen-Nuremberg, Henkestr. 9-11, D-91054 Erlangen, Germany
6Institute of Energy and Climate Research, Forschungszentrum Jülich GmbH, Troposphere (IEK-8), Wilhelm- Johen-Str, D-52428 Jülich, Germany
Abstract
Background
The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling.
Methods
In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA.
Results
In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity.
Conclusion
Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized
