Cellular adhesions to the extracellular matrix (ECM) and to neighboring cells are vital interactions within metazoans. This dissertation examines cellular adhesion by utilizing the adhesive interaction between platelets and collagens that occurs at vascular wound sites and is a crucial step in hemostasis. Platelets are central elements in maintaining an intact circulatory system, but they also have a significant role in thrombotic pathologies such as heart attack and stroke. I analyze the contributions that the two platelet surface receptors, á2â1 integrin (á2â1) and glycoprotein VI (GPVI)/Fc receptor ã-chain (FcRã) complex, make toward the platelets interaction with collagens at vascular wound sites as well as the cooperation of G protein-coupled receptor (GPCR) signaling in the adhesion process. We demonstrate a novel mechanism of modulating the avidity of á2â1 for collagens that causes an increase in platelet adhesion and that is triggered through GPCR and GPVI/FcRã activation of phospholipase C (PLC). A discussion is included on platelet adhesion and signaling involved in hemostasis and thrombosis, substrate/integrin interactions, and anti-platelet therapies.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02182011-143449 |
| Date | 25 February 2011 |
| Creators | Marjoram, Robin James |
| Contributors | Samuel Santoro, Mary Zutter, David Friedman, Billy Hudson, Andries Zijlstra, Jay Jerome |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02182011-143449/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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