Toxinogenicity of Helicobacter pylori in the pathogenesis of chronic gastritis and peptic ulcer and the nature of the host's immune responses

Zhang, Qibo (1997) Toxinogenicity of Helicobacter pylori in the pathogenesis of chronic gastritis and peptic ulcer and the nature of the host's immune responses. PhD thesis, University of Glasgow.

Full text available as:
[thumbnail of scanned version of the original print thesis] PDF (scanned version of the original print thesis)
Download (5MB)
Printed Thesis Information:


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. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Pathology, immunology, microbiology, Helicobacter pylori infections, peptic ulcer, gastritis.
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Russell, Dr. R.I.
Date of Award: 1997
Depositing User: Enlighten Team
Unique ID: glathesis:1997-71779
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 17 Oct 2022 10:23
Thesis DOI: 10.5525/gla.thesis.71779

Actions (login required)

View Item View Item


Downloads per month over past year