Inhibition of parasite growth in chronic Trypanosoma brucei infections

Houston, Julia M. (1997) Inhibition of parasite growth in chronic Trypanosoma brucei infections. MSc(R) thesis, University of Glasgow.

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Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b1680312

Abstract

The objective of this project was to investigate the origin of inhibition of growth of trypanosomes in chronic infections as demonstrated by Turner et al (1996). In order to do so the following strategies were employed; adoptive transfer of splenocytes from chronically-infected to uninfected mice, inhibition of inducible nitric oxide (NO) synthase activity in vivo followed by infection with Trypanosoma brucei and infection of mice lacking inducible NO synthase activity. The origin of growth inhibition was investigated using spleen cell transfer assays with a view to determining whether a putative inhibitory factor might be of parasite or of host origin. In irradiated recipients, spleen cells from trypanosome-infected donors caused inhibition of growth of subsequent infections but this observation was unreliable in repeat experiments. Inability to display a clear trend may have been due to resident macrophages of the recipient immune system being present and active in recipient mice following irradiation. Any effect upon growth of trypanosomes exerted by transferred macrophages in vivo might perhaps have been masked in recipient mice by resident macrophages. In view of the dearth of literature regarding the actions of macrophage-produced NO upon the growth and survival of trypanosomes, the possible involvement of NO in the phenomenon of growth inhibition was investigated. The production of NO was shown to be increased upon infection with Trypanosoma brucei, but to an extent lower by several orders of magnitude than that demonstrated previously. This was concluded to be due to procedural inaccuracies in the work of others. Inhibition of inducible NO synthase activity was found to be without clear effect upon the growth rate of acute-phase trypanosome infections or inhibition of growth of trypanosomes in chronic infection. A trend toward reduction in growth inhibition was demonstrated in mice which had received the iNOS inhibitor L-NAME but this observation was not repeatable. The use of mice genetically manipulated to lack inducible NO synthase activity also failed to demonstrate any effect of NO upon growth inhibition in chronic infections. A reason for my failure to demonstrate a role for NO in regulation of trypanosome growth could be that L-NAME treatment of mice and iNOS gene deletion were found to be ineffective in achieving a state of significantly reduced NO synthase activity in mice. Hence, whilst there was a failure to demonstrate a role for NO in growth inhibition, a lack of involvement for NO was not demonstrated either.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Parasitology, Trypanosoma brucei.
Subjects: Q Science > QR Microbiology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Turner, Professor Mike
Date of Award: 1997
Depositing User: Enlighten Team
Unique ID: glathesis:1997-71359
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 05 Sep 2022 13:02
Thesis DOI: 10.5525/gla.thesis.71359
URI: http://theses.gla.ac.uk/id/eprint/71359

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