NR ATPI
AU Bamme,T.; Riemer,C.; Mok,S.W.F.; Klemm,U.; Baier,M.
TI Chemokine CXCL13 expression in scrapie-infected brain tissue
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-19
PT Konferenz-Poster
AB
The astrocytosis in the scrapie-infected brain 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 the disease progression.
Beside the 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 insights into the functional biology of this chemokine in the CNS and its possible contribution to the scrapie pathogenesis it was decided to generate CXCL13 transgenic mice. We used a vector with a GFAP promoter-expression cassette to facilitate astrocyte-specific CXCL13 expression in the CNS. The murine CXCL13 cDNA with a shortened 3'UTR region was cloned and the human glioma cell line SNB-19 was transfected with this construct. ELISA measurements confirmed high amounts of CXCL13 protein in cell culture supernatants of transfected cells, which were absent in mock-transfected controls. The generation of mice transgenic CXCL13 is presently ongoing.
AD Theresa Bamme, Constanze Riemer, Simon Mok, Michael Baier, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany; Uwe Klemm, MPI für Infektionsbiologie, Diedersdorfer Weg 1, 12277 Berlin, Germany
SP englisch
PO Deutschland