liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Epithelial barrier dysfunction in ileal Crohn's disease
Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study aimed at investigating the intestinal barrier in Crohn's disease, with special reference to epithelial responses to luminal stimuli, and to permeation of proteins.

Ileal mucosa from patients undergoing intestinal resection was studied in vitro in Ussing chambers. Intestinal permeability was also studied in vivo, by oral load of lactulose and mannitol.

The Ussing chamber was evaluated for intestinal barrier studies. Normal ileal mucosa from patients with colon cancer was subjected to long-term experiments, and investigated in regard to various viability parameters. Mucosal permeability, structural integrity and metabolism were maintained for 90 minutes, and specimens with poor viability were detected by a low transepithelial potential difference. In rat ileal mucosa, luminal sodium caprate, a constituent of milk fat, induced dilatation of the tight junctions as visualised by electron microscopy, and a reversible increase in tight junction permeability. The findings indicate that the Ussing chamber is suitable for studies of the intestinal barrier, including tight junction regulation, provided that experiments are monitored by measurements of transepithelial potential difference and are limited in time.

In vitro studies of human ileal mucosa showed that luminal sodium caprate caused uncoupling of oxidative phosphorylation, as shown by a fall in epithelial ATP contents, and mitochondrial swelling seen by electron microscopy, paralleled by an increased permeability. Non-inflamed Crohn's disease specimens had an exaggerated permeability increase and an augmented fall in transepithelial electrical resistance. Confocal microscopy revealed rearrangements of perijunctional filamentous actin, causing dilatation of the tight junctions. In Crohn's disease, a more pronounced reorganisation of actin filaments was seen, suggesting the tight junctions to be hyperreactive to luminal stimuli due to a disturbed cytoskeletal regulation.

In vivo, an increased intestinal permeability was induced by ingestion of acetylsalicylic acid. One third of both Crohn's disease patients and their first-degree relatives showed an augmented permeability increase, whereas spouses were equal to controls, suggesting a genetically determined vulnerability of the intestinal barrier.

In vitro, non-inflamed ileum from Crohn's disease patients had an increased permeation of ovalbumin. Confocal microscopy suggested this to be caused by an augmented transcytosis, a previously unrecognised defect in the epithelial barrier in Crohn's disease, with a subsequent exposure of antigenic proteins to the subepithelial immunocytes.

The Crohn's disease patients without residual inflammation after surgery were followed with endoscopy within twelve months, and all revealed recurrent ileal inflammation.

The study indicates a perturbed intestinal barrier in Crohn's disease, possibly genetically determined. The impaired barrier function is demonstrated both by an augmented epithelial transcytosis and by hyperreactive tight junctions. The epithelial barrier dysfunction precedes the recurrent intestinal inflammation in ileal Crohn's disease. The findings suggest an interplay between an impaired epithelial barrier and luminal factors in the initiation of intestinal inflammation.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1998. , 70 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 578
Keyword [en]
acetylsalicylic add, confocal microscopy, Crohn's disease, cytoskeleton, electron microscopy, genetics, human, ileum, inflammatory bowel disease, intestinal absorption, intestinal mucosa, macromolecules, mitochondria, ovalbumin, permeability, sodium caprate, tight junctions, transcytosis, uncoupling agents, Ussing chamber
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-25636Local ID: 10010ISBN: 91-7219-320-4OAI: diva2:246184
Public defence
1998-12-11, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)

Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.

Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-25Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Dabrosin-Söderholm, Johan
By organisation
SurgeryFaculty of Health Sciences
Medical and Health Sciences

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: 63 hits
ReferencesLink to record
Permanent link

Direct link