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Title: Glucocorticoid modulation of macrophage function
Author: Heasman, Sarah Jane
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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In this thesis, I have examined the effects of glucocorticoid-treatment of peripheral blood monocytes which has previously been demonstrated to markedly augment phagocytic capacity for apoptotic cells, an effect which may contribute to anti-inflammatory actions of glucocorticoids. Within the inflammatory site, the cytokine environment governs the differentiation and function of infiltrating leukocytes. I have investigated the effects of combinatorial treatment of monocytes with the principal Th1 and Th2 cytokines, IFN-γ and IL-4. I have demonstrated that whilst glucocorticoids exert a dominant effect over those of IFN-γ in terms of cell morphology and cell surface receptor expression, glucocorticoid-augmented phagocytosis of apoptotic neutrophils is inhibited by IFN-γ. These findings suggest that the effectiveness of glucocorticoids in promoting a highly phagocytic macrophage phenotype is crucially dependent on the cytokine milieu at inflammatory sites. Cellular migration is an important determinant for the initiation of inflammatory responses and for the resolution phase, where macrophages migrate to draining lymph nodes. My results provide evidence for an alteration in the adhesion and migration of macrophages following glucocorticoid treatment. I have demonstrated changes in cytoskeletal organisation and assembly/engagement of Rho family GTPase signalling pathways. These changes may influence macrophage migration patterns that are important for the progression of inflammatory responses. Together, the studies presented in this thesis suggest that glucocorticoids exert profound effects upon macrophage cytoskeletal organisation that influences both phagocytosis and migration and may also cause a switch in apoptotic cell recognition mechanisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available