Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263002
Title: Toxinogenicity of Helicobacter pylori in the pathogenesis of chronic gastritis and peptic ulcer and the nature of the host's immune responses
Author: Zhang, Qibo
ISNI:       0000 0001 3577 2930
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1997
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Abstract:
Despite the widespread recognition of the role of H. pylori infection in chronic gastritis and peptic ulceration, the mechanisms by which the bacterium induces mucosal damage and the apparent different outcome in infected patients are still not well understood. It has been suggested that the toxinogenicity of H. pylori and the host response may be important in these respects. Neutrophil function is an important host defence mechanism against microbial infection. It provides a major soiirce of reactive oxygen metabolites which are known to cause tissue damage. H. pylori has been shown to activate neutrophils and there are variations among H. pylori strains in the neutrophil activating activity. It is not known if cytotoxin-producing strains of H. pylori are associated with the generation of an oxidative burst in neutrophils. This has been investigated in this thesis. Cytotoxin positive strains of H. pylori displayed an enhanced induction of the oxidative burst in non-opsonised neutrophils compared to toxin negative strains from patients with chronic gastritis only. However, some non-cytotoxin-producing strains also induced a significant neutrophil oxidative burst, suggesting that some component(s) other than cytotoxin itself may be responsible for the induction of the neutrophil oxidative burst. Nevertheless the finding that cytotoxin-producing strains of H. pylori induced an enlianced neutrophil respiratory burst may suggest that the neutrophil activating property may be more strongly expressed in most toxinogenic strains of H. pylori. The ability of some strains of H. pylori to produce cytotoxin and to induce the oxidative burst in neutrophils may be important in the pathogenesis of peptic ulcer disease. Subsequent study investigated the possible component(s) of H. pylori which induces the neutrophil oxidative burst. It was found that soluble products of H. pylori could activate neutrophils to release ROM and more than one bacterial product may be involved in the activation of neutrophils. The results also showed that the neutrophil activating activity was destroyed by proteinase K, suggesting that the active components are mainly proteins. Cytotoxin and urease containing fractions from chromatography did not induce a significant CL response, suggesting that the cytotoxin and/or urease are not the active components for the neutrophil activation. In vitro studies have suggested that toxinogenic strains of H. pylori, which possess CagA(cytotoxin-associated protein) and/or VacA(vacuolating cytotoxin), may induce a more potent inflammatory response, evidenced by an enhanced induction of interleukin 8(IL-8) and neutrophil oxidative burst. It is unclear whether there is any relationship between in vivo mucosal production of IL-8 and neutrophil-derived reactive oxygen metabolites(ROM) release and whether mucosal levels of IL-8 and ROM are increased in those patients infected with toxinogenic strains. It has been shown in this thesis that there is a good correlation between IL-8 concentration and ROM release in antral gastric mucosa. This suggests that local mucosal production of IL-8 in response to H. pylori infection does occur in vivo and may play an important role in attracting and activating phagocytes to release ROM.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.263002  DOI: Not available
Keywords: Microbial infection
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