Toxicology of ultrafine and nanoparticles
Project Leader: Silvia Diabaté
Research Group: Weiss
tel.: +49 721 608 22692 (office) or -26457 (lab)
The causes of adverse health effects due to inhalation of particles are not well understood. This is especially the case for very small particles unintendedly released by combustion processes (ultrafine particles < 100 nm) or produced for special purposes (nanoparticles < 100 nm). Most of the knowledge is based on recent studies on ambient ultrafine particles which are associated with increased respiratory and cardiovascular mortality and morbidity of the general public at elevated concentrations.
The main objectives of our research programme are:
- to identify the physico-chemical parameters of particles which contribute to the adverse health effects by in vitro studies using well defined nanoparticles (hematite, carbon black) and complex combustion derived particles (fly ash).
- to identify the cellular and molecular mechanisms, which initiate and modulate the adverse heath effects.
to establish a lung-specific biotest using exposure of cells at the air- liquid interface to screen the toxicologic potential of unknown aerosols.
Particles are taken up by lung cells and induce local effects by oxidative injury and pulmonary inflammation. This can lead to long-term consequences such as chronic bronchitis (COPD), fibrosis and cancer. Our studies with transmission electron microscopy also showed that all nanoparticles under study were taken up by cells. However, the uptake mechanism is still unknown.
Particles with the ability to generate reactive oxygen species due to their surface properties and/or adsorbed transition metals are most critical since induction of intracellular oxidative stress seems to be a key event of the biological effects of particles. We have recently shown that oxidative stress induced the expression of antioxidant proteins such as heme oxygenase-1 (HO-1) and increased the cellular glutathione content in alveolar and bronchial epithelial cells as well as macrophages after exposure to combustion generated particles. Expression of these genes protects cells from oxidative damage and can prevent mutagenesis and cancer. The transcription factors Nrf2 and AP-1 are most likely involved in activating genes leading to these responses. Although there are extensive studies on this topic using ambient particles, the exact mechanisms of these processes are still unknown. The results of this study help to understand the lung defence against particulate pollutants.
As an alternative to the well-known submerged exposure to nanoparticles, cells can be exposed to an aerosol via the airliquid interface which more resembles the conditions during inhalation of particles and deposition on the lung surface. For this type of experiments a special exposure device is necessary which is operated by the Institute of Technical Chemistry - Thermal Waste Treatment (ITC-TAB). Recent studies showed, that this exposure can be conducted reproducibly for the sub-micron fraction of fly ash particles with regard to the deposition of particles on the cells as well the cell responses.
Other research projects within the Weiss Group
- Molecular toxicology of genotoxins and nanomaterials ( Carsten Weiss, Group leader )