12/2009 Prof. Dr. Gunter Wolf
Role of local Complement Regulators in the Kidney

Abstract:
Complement represents a central part of innate immunity and the multiple components of this defense system contribute to cell integrity and homoeostasis. Mutations in genes coding for complement regulators such as Factor H, Factor I or MCP are associated with renal diseases membranoproliferative glomerulonephritis type II, as well as atypical hemolytic uremic syndrome. Also these regulators are primarily produced and secreted by the liver, recent evidence shows hat local production of these complement components in the kidney by podocytes, endothelial- as well as tubular epithelial cells is central for protection from local complement mediated and inflammatory damage.

In this project we aim to analyze whether murine renal cells, like tubular- and mesangial cells, or podocytes synthesize soluble complement factors (e.g. Factor H), as well as membrane bound complement regulators (e.g. CR1, CR2, Crry). In addition the role of both locally synthesized and that of surface bound complement regulators for protection of renal cells from complement mediated and inflammatory damage will be assayed in vivo. In a murine model for hemolytic uremic syndrome which has been developed in our department antibodies directed against the endothelial surface will be used to assay the effect of this cellular damage on the expression of complement components and regulators in the kidney. The results will help to define the role of locally expressed complement regulators in the kidney and will help to design novel therapies for these severe kidney diseases.

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