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Title: Phagocytic and inflammatory properties of NOD macrophages
Author: Houlberg, Kristian Anthony Niels
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Robust in vitro phagocytosis assays, using either microscopy or flow cytometry were developed and adapted to evaluate phagocytosis of a wide range of particles including apoptotic cells (AC), latex beads and pneumococci . NOD derived Mφ exhibited a marked in vitro phagocytic defect for AC and latex beads but not pneumococci opsonised with IgG. A peritoneal phagocytosis assay was then used to examine phagocytosis of AC and latex beads in vivo. Mathematical modelling of AC and peritoneal Mφ (PMφ) numbers indicated that PMφ fro NOD mice took twice as long to ingest an AC in vivo compared to control C57BL/6 PMφ. Study of peritoneal AC clearance in various NOD congenic strains strongly suggested that the gene(s) responsible for the phagocytic defect were located on idd 18 on chromosome 3. This locus contains the exciting candidate gene Vav3 that is involved in the intracellular regulation of Mφ phagocytosis. The inflammatory phenotypes of bone marrow derived macrophages (BMDMφ), PMφ and pleural Mφ (PLMφ) were then compared. In vitro studies indicated that BMDMφ were hyper-inflammatory whilst resident Mφ were hypo-responsive to the same stimuli compared to control C57BL/6 Mφ. NOD mice recruited fewer leukocytes in both thioglycollate peritonitis and carrageenan pleurisy but no differences in chemokine levels were evident. In contrast to the diminished leukocyte recruitment evident in Mφ dependent models of inflammation. NOD mice were able to mount an extremely vigorous immune response. Thus, although it is relatively straightforward to examine Mφ function in vitro, the analysis of the role of Mφ as co-ordinators of inflammatory response in vivo is much more complex and the mechanisms underlying the diminished leukocyte response of NOD mice in Mφ dependent models of inflammation remain unclear.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available