NR AUSF
AU Riemer,C.; Bamme,T.; Gültner,S.; Heise,I.; Mok,S.W.F.; Baier,M.
TI Chemokine CXCL13 expression in scrapie-infected brain tissue
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Pathogenese/Infektion PATH-06
PT Konferenz-Poster
AB
The astrocytosis in scrapie-infected brain tissue correlates with an extreme upregulation of chemokines, which bind to the receptor CXCR3. One of these induced CXCR3-ligands is CXCL13, in the periphery known to be a chemoattractant for B-cells. CXCL13 mRNA-levels are upregulated at relatively early stages of the disease and show a further increase during disease progression.
Beside detection of upregulated mRNA levels we have established immunohistological methods to demonstrate CXCL13 protein expression in scrapie-infected and uninfected brain tissue. Time course studies revealed a pronounced induction of CXCL13 expression initially in the corpus callosum and cerebellum and in later stages also in the hippocampus and striatum. At the terminal stage of the infection virtually all brain regions are CXCL13-positive. Mock-infected controls showed only a weak constitutive CXCL13 expression in the corpus callosum and cerebellum.
Using a double-staining procedure with anti-GFAP and anti-CXCL 13 antibodies we could show for the first time that CXCL13 is expressed by activated astrocytes in the CNS.
To gain more more insights into the functional biology of this chemokine in the CNS and its possible contribution to the scrapie pathogenesis mice transgenic for CXCL13 were generated. A vector providing a GFAP promoter-expression cassette to facilitate astrocyte-specific CXCL13 expression in the CNS was employed. The murine CXCL13 cDNA was cloned into a vector providing a GFAP promoter-expression cassette facilitating astrocyte-specific CXCL13 overexpression in the CNS. Upon transfection of the human glioma cell line SNB-19 with this construct ELISA measurements confirmed high amounts of CXCL13 protein in cell culture supernatants in transfected but not mock-transfected controls. The generation and characterization of mice transgenic for CXCL13 will be presented.
AD C.Riemer, T.Bamme, S.Gültner, I.Heise, S.Mok, M.Baier, Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany
SP englisch
PO Deutschland
OR Tagungsband