Platelets : their exploitation and elimination

Abstract

Platelets are cytoplasmic fragments present in large numbers within the bloodstream that contain a multitude of proteins. For a long time, platelet function was believed to be limited to the essential functions of haemostasis and thrombosis. However, it has become clear in the last decade that platelets play significant roles in both innate and adaptive immunity, inflammatory responses including leukocyte migration, tissue regeneration and angiogenesis. Parallelling the revelation of the diverse physiological functions of platelets, however, has been the association of exacerbated platelet function with numerous thrombotic and chronic inflammatory diseases. Until our knowledge of platelet biology is more comprehensive, the prevention of platelet-associated pathologies will remain a challenge of inhibiting pathology-associated platelet reactions whilst preserving those essential for normal function. The aims of this thesis, therefore, were to examine in detail the following three platelet-associated biological processes: (i) The role of platelets in tumour cell metastasis, in particular, the kinetics and interrelationship of the pro-metastatic role of platelets and the anti-metastatic role of NK cells, and the relevant contributions to the metastatic process of platelet P-selectin and endothelial P-selectin. (ii) The determinants and mechanisms of antibody-mediated platelet elimination, as seen in the medical condition known as immune thrombocytopenic purpura (ITP), and the role of inhibitory self-recognition systems in this process. (iii) The factors influencing platelet and erythrocyte lifespan by establishing appropriate experimental and analytical methodologies

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