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Immunological and functional consequences of von Willebrand factor binding to complement C1q

Donat, Claudia. Immunological and functional consequences of von Willebrand factor binding to complement C1q. 2020, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13552

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Abstract

Whereas C1q, the pattern recognition molecule of the classical complement pathway, is a crucial player of the innate immune system, von Willebrand factor (vWF) is vital for the initiation of primary hemostasis and functional coagulation.
Although it has been shown that vWF binds to C1q, the impact of the C1q-vWF interaction remains poorly understood.
The reciprocal activation of the complement and coagulation systems has been increasingly shown not only in health but also in a growing number of inflammatory diseases, but the precise pathogenic mechanisms are still incompletely clarified.
Therefore, we aimed at determining the implications of the C1q-vWF binding:
In a first study, we elucidated the interaction between C1q and vWF in the context of atherosclerosis. By using complexes of cholesterol crystals, C1q and vWF as an in vitro model, we were able to demonstrate that these complexes decrease phagocytosis and secretion of inflammatory cytokines by human macrophages. In this way, our results show that C1q-vWF formation could have a favorable effect in an atherosclerotic setting.
In a second study, we examined the interaction between C1q and vWF in the context of hemostasis. By performing quantitative and functional hemostatic tests in C1q-deficient mice, we were able to demonstrate that C1q enhances primary hemostasis, potentially in a vWF-dependent manner.
These findings suggest that C1q exerts a hemostasis-mediating role and provide a possible explanation for thromboembolic complications in inflammatory disorders.
In conclusion, both studies contribute to a better understanding of the C1q-vWF interaction and point towards an impact in atherosclerosis and hemostasis.
Advisors:Trendelenburg, Marten and Skoda, Radek Ctirad
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Immunology (Trendelenburg)
05 Faculty of Science
UniBasel Contributors:Trendelenburg, Marten
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13552
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (VI, 65, lix Seiten)
Language:English
Identification Number:
Last Modified:17 Jun 2020 04:30
Deposited On:16 Jun 2020 12:12

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