PECAM-I is a 130kDa member ofthe immunoglobulin superfamily, expressed on the surface ofhaematopoietic cells. The cytoplasmic tail contains two immullOreceptor tyrosine based inhibition motifs which can mediate both stimulatory and inhibitory signals. The aim of this thesis is to investigate the function of PECAM-I in the regulation of platelet activation and fonnation. Using PECAM-Io/' mice and cross-linking of PECAM-I using specific antibodies, I demonstrate a minor inhibitory role on platelet responses to the collagen receptor GPVI, the integrin allb~3 and the C-type lectin receptor CLEC-2. Furthennore, the degree of inhibition is considerably less than that produced by P0I2Ã?Â? This weak inhibitory effect ofPECAM-1 on platelet activation indicates that PECAM-I is not a major regulator of platelet activation. Further research reveals an important role in thrombopoiesis. Following induced thrombocytopenia, recovery . . of the peripheral platelet count is impaired in PECAM-l'' mice. A migration defect in PECAM-l'' megakaryocytesis identified in response to a gradient of SDFla. These observations are confinned in vivo with the demonstration of altered spatial localisation of megakaryocytes within the bone marrow in PECAM-Io/- mice. A further chapter considers the various approaches that could be used to establish the molecular basis ofthis effect.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:487509 |
| Date | January 2007 |
| Creators | Dhanjal, Tarvinder Singh |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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