Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.693341
Title: The role of GPVI and CLEC-2 in platelet activation by miscellaneous ligands
Author: Alshehri, Osama Mohammed D.
ISNI:       0000 0004 5922 5212
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2016
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Abstract:
Platelets are an essential factor in wound repair and blood clotting, where exposed sub-endothelial extracellular matrix (ECM) proteins induce activation during vascular injury. However, platelets can also be activated by a diverse range of stimuli that share little-to-no resemblance in structure to each other, or to recognized ligands of platelet receptors. These stimuli include diesel exhaust particles (DEP), various peptides including 4N1-1 and Champs, lipoproteins such as PAM3-CSK4, and large polysaccharides for example, fucoidan, and dextran. In this thesis, I demonstrate that this seemingly miscellaneous group of stimuli cause aggregation of human and mouse platelets through Src and Syk tyrosine kinases in association with stimulus-specific tyrosine phosphorylation of the GPVI/FcRγ-chain complex and/or CLEC-2. A critical role for GPVI and/or CLEC-2 in mediating aggregation is shown using platelets from receptor-deficient mouse platelets. Additionally, in double deficient mouse platelets these stimuli activate Src tyrosine kinases independent of GPVI and CLEC-2. DEP, fucoidan and dextran were shown to activate transfected GPVI or CLEC-2 in a cell line model. However, 4N1-1, Champs and PAM3-CSK4 did not activate transfected GPVI or CLEC-2 in a cell line model, nor could they bind to recombinant forms of either receptor. In addition, I demonstrate the unexpected observation that fibrin also activates GPVI revealing a new stage of haemostasis in which the generation of fibrin from fibrinogen reinforces platelet activation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.693341  DOI: Not available
Keywords: QH301 Biology
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