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A1929 - Correlation of Ambient Particle Characteristics and Adverse Effects of Reactive Oxygen Species (ROS) to Normal and Diseased Airway Epithelia
Author Block: Z. Leni1, L. Cassagnes2, I. Haddad2, N. Baumlin3, M. A. Salathe4, U. Baltensperger2, J. Dommen2, M. Geiser5; 1Institute of Anatomy, University of Bern, Bern, Switzerland, 2Laboratory of atmospheric chemistry, Paul Scherrer Institute, Villigen, Switzerland, 3Division of pulmonary critical care and sleep medicine, University Miami, Miller school of medicine, Miami, FL, United States, 4Univ of Miami Sch of Med, Miami, FL, United States, 5Institute of Anatomy, Univ of Bern, Bern CH-3012, Switzerland.
Rationale: The mechanisms of how exposure to airborne particulate matter (PM) leads to pulmonary pathology remain still poorly understood. Reactive oxygen species (ROS), generated from redox cycling of organic compounds and transition metals of PM at the air liquid interface (ALI), are considered to play a central role in causing the observed adverse effects. We tested the hypothesis that PM disrupts lung epithelial integrity via enhanced oxidative stress. Exploring the dependence of ROS formation on the abundance of transition metals in PM10 and PM2.5 is decisive to understand the influence of PM on human health. Methods: Two chemical compounds, representative for different aerosol constituents, were applied to the ALI of differentiated human bronchial epithelial cell cultures: Firstly, we used 1,4-naphthoquinone (1,4-NQ), a polycyclic aromatic quinone emitted as a combustion product of fossil fuel or formed in the atmosphere by photochemical reactions of polycyclic aromatic hydrocarbons. Secondly, we used CuCl2, one of the trace metal constituents of PM. Furthermore, cells were exposed to aqueous filter extracts of PM10 and PM2.5, collected in rural and urban parts of Switzerland during the winter and summer of 2013 and 2014. The capacity of PM to oxidize target molecules was assessed by acellular measurements of the oxidative potential (OP) and metals by ICP-MS on monthly composites. Cell cultures were exposed to various doses of these compounds and to filter extracts for 4 h. Cellular responses were measured 24 h post-exposure. Results and Conclusion: Significantly higher cytotoxicity was observed after exposure of diseased epithelia to 1,4-NQ and CuCl2 in comparison to exposures of normal cells (i.e., 50% vs. 25%, respectively). Furthermore, exposure to a combination of 1,4-NQ and CuCl2 revealed a synergistic effect regarding cytotoxicity in both epithelia, but the effect was 1.36-fold higher in normal compared to diseased epithelia. OP obtained from filters differed between sites and seasons. PM from urban areas showed higher OP than PM from rural sites (3.1 and 4.5 fold higher for winter and summer, respectively). Total metal mass was higher in PM10 versus PM2.5 filters and higher in urban compared to rural sites (1.9-9.5 fold). The highest concentration of metals was obtained for the redox active Fe (242.8-1486.9 ng/m3), Cu (12.2-74.7 ng/m3) and Zn (11.3-42.2 ng/m3). These results show that particle surface components participating in redox cycling generate ROS, which are responsible for adverse effects to bronchial epithelia. This abstract is funded by the SNF grant CR32I3_166325.