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Selected Publication:
Artinger, K.
IN SEARCH FOR NEW THERAPEUTIC APPROACHES IN KIDNEY DISEASE: INVESTIGATIONS INTO THE ROLE OF THE SPLEEN IN NEPHROTOXIC SERUM NEPHRITIS
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2017. pp.
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- Authors Med Uni Graz:
- Advisor:
- Eller Kathrin
- Rosenkranz Alexander
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- Abstract:
- Introduction: Despite the availability of different treatment options, many people suffering from glomerulonephritis today still face the burden of end stage renal disease. Experimental models like the model of nephrotoxic serum nephritis (NTS) serve as tools for the evaluation of possible new treatment targets. In NTS, secondary lymphoid organs are recognized as places of immune regulation. Although the lymph node has been well characterized as such, the role of the spleen in this model was incompletely understood so far. Therefore, this work aimed to elucidate the functional and structural changes in the spleen in the course of NTS, as well as the effect of splenectomy in this model. Methods: Healthy C57BL/6 mice and mice with NTS on day 14 and day 28 were evaluated for histopathology and spleen infiltrating cells. Flow cytometric data for haematopoietic precursors of healthy, immunized and nephritic mice on day 14 were evaluated. Further, mice were splenectomised or sham-operated and subsequently NTS was induced. Results: Anaemia and a gradual enlargement and weight gain of the spleen were seen over the course of NTS until day 14. However, splenectomised and sham-operated mice did not show differences in albuminuria on day 7 and day 14 and PAS-positivity in glomeruli. In line, numbers of kidney infiltrating CD4+ and CD8+ T cells, CD68+ macrophages as well as Ly6G+ neutrophils were unchanged between the two groups. Also serum anti-rabbit IgG did not differ between splenectomised and sham-operated nephritic mice. The enlargement and increase in spleen weight was not attributable to CD4+CD69+ and CD8+CD69+ leukocytes as measured by quantitative flow cytometry. Immunohistochemical stainings of spleens for F4/80+ cells showed a marked increase of the red pulp. Finally, extramedullary haematopoiesis was detected by means of immunohistochemical stainings for CD41 and Ter119. Flow cytometric analysis provided evidence of erythroid cell increase in the spleen depending on the CXCR4/CXCL12 axis. Further, immunized and nephritic mice displayed increased levels of serum IFN-¿, Il-6 and TNF-a. Conclusion: The spleen is not essential for the development of NTS, but is a place of extramedullary haematopoiesis in this model. Proinflammatory cytokines like IFN-¿ contribute to this process by means of suppressive activity on the bone marrow.