Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663294
Title: Characterisation of the molecular mechanism of CD44 augmented macrophage phagocytosis of apoptotic neutrophils
Author: Vivers, S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
To further characterise the mechanism of cross-linking of CD44 on macrophage phagocytosis, cation depletion studies were carried out. Data presented in this thesis demonstrates that augmentation of phagocytosis following CD44 cross-linking involved two components. This observation suggested that CD44 cross-linking results in augmentation of macrophage phagocytosis, which has both a cation dependent and cation independent component. Depletion of divalent cations reduces the level of CD44 augmented phagocytosis but does not entirely block it. Treatment of macrophages with a variety of inhibitors and antibodies allowed identification of the molecule responsible for the cation dependent component _CD32 (FcγRII). CD44 antibodies were shown to be acting as a bridge between CD32 on the apoptotic neutrophil and CD44 on the macrophage. This highlighted the importance of using F(ab’)2 fragments instead of whole antibodies for functional studies. To investigate potential signalling mechanisms resulting in CD44 augmented phagocytosis anti-CD44 F(ab’)2 fragments were generated and conjugated to 6μm beads, which were used to cross-link CD44 on the macrophage surface. Immuno-fluorescent microscopy was then used to image changes in cellular distribution of signalling molecules in response to CD44 cross-linking. The data presented in this thesis implicates redistribution of ezrin, actin, PKC and Rac2 in the augmentation of macrophage phagocytosis of apoptotic neutrophils following CD4 cross-linking. Western blot and inhibition studies indicated that ERK did not play a role in CD44 augmented phagocytosis. In summary, the studies presented in this thesis represent an analysis of the cellular and molecular events associated with augmentation of phagocytosis of apoptotic neutrophils. These studies provide a firm foundation for future studies and highlight the potential for modulation of phagocyte capacity for clearance of apoptotic cells in treatment of inflammatory disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.663294  DOI: Not available
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