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Von Willebrand factor binds surface-bound C1q and induces platelet rolling

Kölm, Robert. Von Willebrand factor binds surface-bound C1q and induces platelet rolling. 2015, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_11316

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Abstract

Pre-mature atherosclerosis and thrombotic complications are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the high incidence of these complications cannot be explained by traditional risk factors alone suggesting direct effects of an activated immune system on hemostasis.
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.
Advisors:Palmer, Ed
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)
Item Type:Thesis
Thesis no:11316
Bibsysno:Link to catalogue
Number of Pages:44 Bl.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:58
Deposited On:02 Sep 2015 13:58

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