The aims of the research presented in this thesis were concerned with investigating the effect of inducible nitric oxide (NO) synthase expression during Trypanosoma brucei infections on both host and parasite. NO was shown to exhibit a potent cytostatic effect on parasite proliferation. Oxyhaemoglobin is a potent scavenger of NO. The cytostatic effects of NO on the trypanosomes were completely prevented through the addition of erythrocytes to the cultures. This implies that in the host blood-stream, NO is unlikely to be involved in the eradication of the parasites. Through the adoptive transfer of suppressor macrophages from T.brucei-infected donor mice to naive recipients, it was demonstrated that NO mediates a suppressive effect on host lymphocyte responses in vivo. Furthermore, suppressor macrophages were shown to have a finite life-span and undergo NO-mediated apoptosis. Evidence also suggested that elevated NO production in the bone marrow of T.brucei -infected mice is likely to play a significant role in the anaemia resulting from T.brucei infection. Experiments demonstrated that a soluble lysate prepared from freeze-thawed blood-stream form T.brucei, activated interferon (IFN)-gamma primed macrophages to express high levels of NO synthase. Experiments also demonstrated that viable blood-stream forms, but not procyclic form trypanosomes, released a soluble factor which in combination with IFN-gamma induced NO synthase. The absolute requirement of IFN-gamma priming for NO synthase activation by T.brucei was studied using macrophages from mutant mice lacking functional IFN-gamma receptors (IFN-gamma R -/- mutant mice). In comparison to macrophages from wild-type mice, cells from IFN-gamma-R-/- mutant mice were unable to produce NO following stimulation in vitro or infection in vivo. Finally, utilising mice with specific immunodeficiencies it was demonstrated that natural killer cells and a/b T-lymphocytes were important sources of IFN-gamma during murine T.brucei infections.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:294456 |
| Date | January 1995 |
| Creators | Mabbott, Neil A. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU543723 |
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