Institute of Lung Biology and Disease (iLBD)

Fine and ultrafine aerosol particles from ambient sources as well as engineered nanoparticles have been shown to cause oxidative stress, to upregulate defense systems and to induce inflammatory reactions in cells of the respiratory epithelium as a primary target of inhaled particulate matter. Alveolar macrophages, pulmonary epithelial cells and invaded neutrophils as part of the innate immune system might be modified in their basic functions by aerosol particles leading to altered immune responses. The mechanism of particle interference with target cells and the impact on regulatory and functional pathways are poorly understood.

Our main focus in research addresses effects of sub100nm particles on redox processes in cell free and cellular systems. To this end we study effects on gene expression, mechanisms of detoxification, stress signaling pathways, inflammation and on lipid mediators as highly potent immunologic regulators.

Two methodological approaches are applied to elucidate basic responses of target cells emerging from interaction with particles:

1. exposure of submerged cell systems to resuspended particles [1, 2] and
2. exposures exposure of cell systems to airborne particles at the air-liquid interface (ALI) [3].

Monocultures and cocultures are used for example to study the impact of macrophage-epithelial cell interactions. The latter approach has been recently established to virtually reflect the situation in the lower respiratory tract.

For investigations we use 2 different exposure scenarios,

1. intratracheal instillation and
2. whole body inhalation exposure of mice. For its practicalness particle instillation is most commonly used to study dose response relations of different kind of particles.

This approach allows us to gain an insight into the importance of certain particle specific properties on the inflammatory response caused [4]. Inhalation exposure on the other hand represents the more realistic exposure scenario und is therefore used to identify health effects and analyze their underlying pathomechanisms [5]. Further we use genetic modified mouse models, in particular so called knock out strains, to study pathways of genetic or acquired susceptibility for particle exposure related diseases.

Literature

[1] Kim YM, Reed W, Lenz AG, Jaspers I, Silbajoris R, Nick HS, Samet JM. Ultrafine carbon particles induce interleukin-8 gene transcription and p38 MAPK activation in normal human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L432-41.

[2] Beck-Speier I, Dayal N, Karg E, Maier KL, Schumann G, Schulz H, Semmler M, Takenaka S, Stettmaier K, Bors W, Ghio A, Samet JM, Heyder J. Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles. Free Radic Biol Med. 2005 Apr 15;38(8):1080-92.

[3] Bitterle E, Karg E, Schroeppel A, Kreyling WG, Tippe A, Ferron GA, Schmid O, Heyder J, Maier KL, Hofer T. Dose-controlled exposure of A549 epithelial cells at the air-liquid interface to airborne ultrafine carbonaceous particles. Chemosphere. 2006 Dec;65(10):1784-90

[4] Stoeger T, Reinhard C, Takenaka S, Schroeppel A, Karg E, Ritter B, Heyder J, Schulz H. Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. Environ Health Perspect. 2006 Mar;114(3):328-33.

[5] André E, Stoeger T, Takenaka S, Bahnweg M, Ritter B, Karg E, Lentner B, Reinhard C, Schulz H, Wjst M. Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung. Eur Respir J. 2006 Aug;28(2):275-85. Epub 2006 Apr 26.