The long-term goal of this project is to investigate uptake and processing of metals by dendritic cells (professional antigen-presenting cells) and osteoclasts (bone resorbing cells). These cells are closely related, specialized macrophages and probably the most important cells in processing pure metals and metal salts in the context of an immune reaction. Aluminum, chromium and titanium will be used as model metals, as they are extensively used in modern daily life and in biomedicine, and as they induce immunopathological reactions (allergies). Little is known about uptake and processing of the metals by the cells, which is mainly due to technical and methodological limitations in detecting and tracking metals at a sub-cellular level. Therefore, using state-of-the-art instruments and microscopic techniques (confocal scanning laser microscopy, FESEM: field emission scanning electron microscopy, EFTEM: energy-filtering transmission electron microscopy, EELS: electron energy-loss spectroscopy and SIMS: secondary ion mass spectrometry) new sample processing methods and detection techniques will be elaborated for detection and tracking of these metals in dendritic cells and osteoclasts. In addition, using a human in vitro cellular immunology model, the functional and immunological relevance of metal processing by the cells will be evaluated. For that purpose, chromium-specific T-lymphocytes and recombinant HLA-tetramers will be used for testing presentation of antigenic chromium by dendritic cells.
