Abstract 99. Jahrestagung der DOG, 29. 9. - 2. 10. 01 im ICC, Berlin

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Kinetics of C-erbB oncoprotein and CD44 isoform expression in the IRBP induced Experimental Autoimmune Uveitis (EAU)

1Stiemer R. H., 1Fischer-Lamprecht C., 2Wiggert B., 3Zöller M., 4Günthert U., 1Zierhut M.

1Dept. of Ophthalmology, University of Tübingen, Germany; 2National Eye Institute, Bethesda, MD, USA; 3German Cancer Research Center, Heidelberg; 4Basel Institute for Immunology, Switzerland

Purpose: Overexpression of oncogen receptor c-erbB-2 in tumors and functional involvement of CD44 isoforms in inflammation, autoimmune diseases and tumors have initiated our analyses concerning their expression in the IRBP induced EAU.
Methods: B10.A mice were immunized subcutaneously with 50µg of IRBP. Immunohistochemical analysis of the eyes was achieved from animals sacrificed on day 10, 18, 24 and 28 (n=5 for each time point). Applied mAbs were directed against c-erbB-2, standard CD44 (CD44s, two different epitopes), splicing variants v7 (exhibiting inhibitory functions in different experimentally induced autoimmune diseases) and v10. Staining was performed using the alkaline-phosphatase method with Neufuchsin as chromogen. Control staining was achieved on eyes omitting IRBP in the immunization protocol and on murine tongue sections.
Results: C-erbB oncogen receptors 2 were expressed in the ciliary body, RPE, around the optic nerve and venules localized in different retinal cell layers. Aquivalent results were observed for CD44s and CD44v7. More staining was observed in retinal destruction which continously was reduced until reaching uninflamed tissue. No expression was observed for CD44v10. While CD44s and CD44v7 peaked on day 18 and decreased by day 28, c-erbB-2 was maximally expressed on day 24 after immunization. Control eyes exhibited significantly reduced staining.
Conclusion: The distinct expression of CD44v7 in EAU may be important in the interaction between Th1 cells and macrophages and their survival as it has been analysed for different murine Th1 dependent autoimmune diseases. Low level expression of c-erbB-2 and CD44 in control eyes indicates that these proteins are not newly synthesized but are stronger expressed under pathological conditions. Functional association of CD44 isoforms and c-erbB oncogen-receptors and their role in cell biology and immunopathology of uveitis will be discussed.
Support: ƒortuene grant 114, DFG-grant ZI 350/13.




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