Kölm, Robert. Von Willebrand factor binds surface-bound C1q and induces platelet rolling. 2015, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11316
The sequence homology between SLE patient-derived autoantibodies against complement C1q (Fab anti-C1q) and von Willebrand factor (vWF) suggested an interaction between the complement and hemostatic system on the level of initiating molecules.
vWF was found to bind to surface-bound C1q under static conditions. The binding was specifically inhibited by Fab anti-C1q and C1q-derived peptides. Under shear stress the C1q-vWF interaction was enhanced, resembling the binding of vWF to collagen I. In addition, I could show that C1q-vWF complexes induced platelet rolling and firm adhesion. Furthermore, I observed vWF binding to C1q-positive apoptotic micro particles and increased vWF deposition in C1q-positive glomeruli of SLE patients compared to control nephropathy.
I show for the first time binding of vWF to C1q and thus a direct interaction between starter molecules of hemostasis and the complement system. This direct interaction might contribute to the pathogenic mechanisms in complement-mediated, inflammatory diseases.
|Committee Members:||Trendelenburg, Marten and De Libero, Gennaro|
|Faculties and Departments:||03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||44 Bl.|
|Last Modified:||30 Jun 2016 10:58|
|Deposited On:||02 Sep 2015 13:58|
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