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Angela Roesen-Wolff
Characterization of the molecular mechanisms that influence phagocyte functions
Previous and current research
Phagocytes are large white cells that engulf and digest marauding microorganisms and other antigenic particles. Important phagocytes are monocytes and macrophages. Monocytes circulate in the blood, then migrate into tissues whereby they develop to macrophages. Macrophages are seeded throughout the body tissues in a variety of guises. Specialised macrophages include alveolar macrophages in the lungs, mesangial phagocytes in the kidneys, microglial cells in the brain, Kupffer cells in the liver, and osteoclasts in bone. Impairment of monocyte functions leads to a variety of human diseases, some of which have been studied by my group: Chronic granulomatos disease (CGD), a defect of NADPH oxidase in neutrophils and monocytes, which leads to a severe immunodeficiency; Tumor necrosis factor alpha receptor associated periodic syndrome (TRAPS), Cryopyrin associated periodic fever syndrome (CAPS), Caspase-1 associated fever syndrome (ICE-fever) which are associated with periodic fever and autoinflammatory disease; and Interferon-gamma receptor deficiencies leading to severe infections with atypical mycobacteria.
Fig.1 This figure shows human osteoclast-like cells (multinucleated giant cells) derived from monocytes by M-CSF and RANKL incubation after 10 days of culture on glass slides. Immunofluorescence DAPI (blue) staining of nuclei and phalloidin (green) staining of actin.
Future prospects and goals
Future projects will deal with the identification of cellular mechanisms which are involved in pathogenesis of the diseases mentioned above: The role of monocytes in granuloma formation in CGD will be characterized in an in vitro model and the formation of endosomes in interferon-gamma receptor deficient cells will be studied. The role of caspase-1 mutations in autoinflammatory disease will be another focus. In addition the cell biological characterization of remodelling of bone by osteoclasts is another main future project. In this connection the influence of bone matrix proteins on these cells is of special interest.
Goals
The goal of our studies is to understand the various functions of phagocytes in different tissues on a molecular level in order to develop novel approaches to therapy of diseases which are caused by impairment of phagocyte functions.
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Selected publications
Rösen-Wolff A, Kreth HW, Hofmann S, Hoehne K, Heubner G, Möbius D, Zintl F, Gahr M, Roesler J (2001). Periodic fever (TRAPS) caused by mutations in the TNFα Receptor1 (TNFRSF1A) gene of three german patients. Eur J Hematol 67: 105-109.
Khattak S, Darai G, Rösen-Wolff A (2004). Puumala virus nucleocapsid protein expressed in transgenic plants is not immunogenic after oral administration. Virus Genes 29:109-116.
Domaschke H, Gelinsky M, Burmeister B, Reinstorf A, Fleig R, Hanke T, Pompe W, Rösen-Wolff A (2006) In vitro ossification and remodelling of mineralized collagen I scaffolds. Tissue Eng 12:949-58
Ryser M, Ugarte F, Thieme S, Bornhäuser M, Rösen-Wolff A, Brenner S (2008). mRNA transfection of CXCR4-GFP fusion – simply generated by PCR – results in efficient migration of primary mesenchymal stem cells. Tissue Eng (in press).
Rösen-Wolff A, et al. (2008) Mutated, structurally altered caspase-1 with decreased enzymatic and increased RIP2 mediated inflammatory activity leads to a new type of periodic fever (ICE fever). Submitted.