Work Package 2
Health Effects and Toxicology of Reactive Organic Compounds in Aerosols
In WP II the biological effects of the freshly generated combustion aerosol, the particle phase alone (stripped with gas phase denuders) and the gas phase alone (filtered) are studied comparatively in human cell systems. The cells are exposed to the aerosol both in vitro and in an exposure equipment at the air-liquid-interface. In co-cultures of up to five cell types are combined to a differentiated human lung tissue model. With in vivo studies the results are transferred to human specimen. The biological effects in cell cultures and tissues are investigated on all hierarchical levels (genome, transcriptome, proteome and metabolome).
Since the emission sources are heavy location-based structures (test benches for diesel and gasoline engines, marine engines and boilers), test aerosol generators and exposure systems are set up mobile. All working groups involved in the HICE virtual institute meet for several large-scale experiments at the various locations in Europe.
The biological effects are examined together with WP III. The biological endpoints therefore are e.g. cytotoxicity, metabolic activity, determination of functions, oxidative stress and inflammatory response markers. In addition, non-targeted effects are addressed by e.g. the basis of genome-wide gene expression, protein profiles and induction analyses. In selected experiments, stable isotope labeling is used to perform flux analyses in proteome and metabolome.
The clinical partners provide human cells and tissue from lavage, biopsy or pathological examination of healthy and diseased persons to search for biomarkers found in the laboratory experiments.
In cooperation with WP IV the data are evaluated and analyzed for biomarkers associated with exposure and harm.