LAUSR

Ultrafine particles (UFP), diameter of <0.1 µm, contribute to urban particulate air pollution. There is still not much evidence on their effects on humans. Our study aims to address their possible effects on lung metabolome.  Alveolar epithelial cells (A549) together with macrophages (THP-1) were seeded on the apical side of the insert membrane, and fibroblasts (MRC-5) on the downside, respectively. Triple cell cultures were exposed at the air liquid interface to different aerosols generated by a combustion aerosol standard (CAST) soot generator. Applied aerosols consisted of UFP with either high or low content of semi-volatile organic compounds (SVOC). Herein, apical cell lysates were extracted for metabolites. Data acquisition was performed by GC-MS and processed with R and then analyzed by MetaboAnalyst. Statistical analysis showed that top features differentiating the high SVOC from clean air controls were amino acids (L-tryptophan and L-lysine), whereas for low SVOC, 5-methylthioadenosine and 5-methoxyindoleacetate. Tryptophan and its metabolite 5-hydroxy- tryptophan were significantly upregulated in high SVOC. However, in low SVOC, 5-methoxyindoleacetate was substantially upregulated. Pathway analysis revealed that purine metabolism was between the top significant enriched pathways in both high and low SVOC groups. Moreover, tryptophan metabolism which modulates immunity and inflammation was enriched similarly in both groups. These findings suggest that lung cell metabolome is modulated distinctively based on the chemical identity of UFP, which could give more understanding about the lung response mechanism to inhaled UFP. This work was funded by Bayerische Staatsministeriums für Umwelt und Verbraucherschutz (BayUFP).