Change search
ReferencesLink to record
Permanent link

Direct link
Cultured human gastric explants: a model for studies of bacteria-host interaction during conditions of experimental helicobacter pylori infection
Umeå University, Faculty of Medicine, Department of Odontology.
Show others and affiliations
2002 (English)In: Journal of infectious diseases, ISSN 0022-1899, Vol. 186, no 3, 423-427 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 186, no 3, 423-427 p.
URN: urn:nbn:se:umu:diva-2507OAI: diva2:140667
Available from: 2003-10-22 Created: 2003-10-22 Last updated: 2011-03-30Bibliographically approved
In thesis
1. Helicobacter pylori: bacterial adhesion and host response
Open this publication in new window or tab >>Helicobacter pylori: bacterial adhesion and host response
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The gastric pathogen Helicobacter pylori infects more than half of the population worldwide. H. pylori manage to establish persistent infection, which would be life-long if not treated. In order to establish such an infection, this pathogen has to deal with the host immune system. H. pylori has certain characteristics which make the bacteria less announced to the host immune system. Additionally, for remaining in the harsh and acidic environment of the stomach with peristaltic movements and a high frequency of turnover of epithelial cells, H. pylori has developed different binding modes to structures present both in the mucus and on the surface of gastric cells and also to extracellular matrix proteins. Evidently, adhesion has a determinant role for a successful colonization by H. pylori. It has been shown that a small fraction of the H. pylori infection is in intimate contact and attached to the host epithelium. Despite its small proportion, this group maintains the persistency of infection. As there is no suitable in vitro system to mimic the human stomach for studies of H. pylori infection, we have developed the In Vitro Explant Culture technique (IVEC). By using this model we could show that H. pylori use the Lewis b blood group antigen to bind to the host gastric mucosa, during experimental conditions most similar to the in vivo situation. Furthermore, we could show that the host tissue responses to the bacterial attachment by expression of Interleukin 8 (IL- ), which will guide the inflammatory processes. Interestingly, by inhibition of bacterial adhesion through receptor competition i.e., by use of soluble Lewis b antigen, IL-8 production was hampered in the IVEC system, which further validates the presence of a tight relation between bacterial adhesion and induction of host immune responses. One of the inflammation signaling cursors in vivo is the upregulated sialylated Lewis x (sLex) antigen, an inflammation associated carbohydrate structure well established as a binding site for the selectin family of adhesion molecules. We could show that during chronic gastric inflammation, which is actually caused by the persistent H. pylori infection, the bacterial cells adapt their binding mode, and preferentially bind to sLex, which will provide an even more intimate contact with the host cells. This interaction is mediated by SabA, the H. pylori adhesin for sialylated oligosaccharides/glycoconjugates. By employing red blood cells as a model we could further demonstrate that SabA is identical to the “established” H. pylori hemagglutinin. We could also show that SabA binds to sialylated glycolipids (gangliosides) rather than glycoproteins on cell surfaces. Our result also revealed that SabA also binds to and activates human neutrophils. Such effect was unrelated to BabA and the H. pylori Neutrophil Activating Protein (HP- AP), which were not directly involved in the activation of neutrophils. Furthermore, phagocytosis of bacteria by neutrophils was demonstrated to be mainly dependent on presence of SabA. Interestingly, HP-NAP showed a possible role in guiding the bacterial adhesion during conditions of limited sialylation, i.e. equivalent to mild gastritis, when the tissue would be less inflamed and sialylated. In conclusion, H. pylori adhesion causes host tissue inflammation, then the bacteria will adapt to the new condition and bind to epithelial cells in a tighter mode by synergistic activities of BabA and SabA. Additionally, SabA bind to and activate human neutrophils, which will exacerbate inflammation responses and cause damage to host tissue. Thus, BabA and SabA are potential candidates to be targeted for therapeutic strategies against H. pylori and gastric disease.

41 p.
Umeå University odontological dissertations, ISSN 0345-7532 ; 82
Communicable diseases, Infektionssjukdomar
National Category
Infectious Medicine
urn:nbn:se:umu:diva-133 (URN)91-7305-537-9 (ISBN)
Public defence
2003-10-29, Umeå, 09:00 (English)
Available from: 2003-10-22 Created: 2003-10-22 Last updated: 2010-02-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Search in DiVA

By author/editor
Borén, Thomas
By organisation
Department of Odontology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 33 hits
ReferencesLink to record
Permanent link

Direct link