Gastroenterology

Gastroenterology

Volume 117, Issue 1, July 1999, Pages 65-72
Gastroenterology

Alimentary Tract
Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?,☆☆

https://doi.org/10.1016/S0016-5085(99)70551-2Get rights and content

Abstract

Background & Aims: Crohn's disease (CD) is associated with a disturbed intestinal barrier. Permeability studies have focused on inert molecules, but little is known about transepithelial transport of macromolecules with antigenic potential in humans. The aim of this study was to quantify permeation and to characterize passage routes for macromolecules in ileal mucosa in CD. Methods: Noninflamed and inflamed ileal mucosa specimens from patients with CD (n = 12) and ileal specimens from patients with colon cancer (n = 7) were studied regarding transmucosal permeation of ovalbumin, dextran (mol wt, 40,000), and 51Cr-EDTA for 90 minutes in vitro in Ussing chambers. Transepithelial passage routes for fluorescent ovalbumin and dextran 40,000 were investigated by confocal microscopy. Results: Noninflamed ileum from CD patients showed increased permeation of ovalbumin compared with ileum from colon cancer patients (P < 0.05). Dextran permeation was equal in the three groups, whereas 51Cr-EDTA permeability was increased in inflamed ileum. Ovalbumin passed both transcellularly and paracellularly, but dextran followed a strictly paracellular route. Both markers were subsequently endocytosed by cells of the lamina propria. Conclusions: Noninflamed ileal mucosa from patients with CD shows increased epithelial permeability to ovalbumin, probably by augmented transcytosis. This increase in antigen load to the lamina propria could be an initiating pathogenic event in CD.

GASTROENTEROLOGY 1999;117:65-72

Section snippets

Patients and endoscopy

Mucosal specimens from the terminal ileum in 12 patients with ileal CD and 7 patients who underwent right hemicolectomy for colonic cancer were investigated. Patient data are given in Table 1.

. Characteristics of patients in the study

Empty CellCD (n = 12)Colon cancer (n = 7)
Age (yr)a40 (19–60)67 (50–76)
Sex (M/F)7/54/3
Disease location
 Ileum10Tumors in the cecum or ascending colonb
 Ileum and colon2
Disease duration (yr)a13 (1–24)
Previous bowel resection70
Medication
 None42
 Steroids ± mesalamine70
 Azathioprine10
 

Characterization of specimens by electrophysiology and morphometry

PDt at the start of the experiments was above 6 mV in 11 (85%) of 13 specimens of noninflamed mucosa from CD patients, in 23 (72%) of 32 specimens from inflamed CD mucosa, and in 21 (88%) of 24 specimens from colon cancer patients. This yielded the following material for the study: 11 noninflamed ileal specimens from 5 patients with CD, 23 inflamed ileal specimens from 8 patients with CD, and 21 ileal specimens from 7 patients with colon cancer (both noninflamed and inflamed mucosa were

Discussion

This is the first study of epithelial permeability to protein-sized macromolecules in the ileal mucosa in CD. Our data suggest that noninflamed ileal mucosa in patients with CD has a previously unrecognized increase in protein permeation. An increased transmucosal permeability to undegraded ovalbumin was seen in the noninflamed ileal mucosa from patients with CD compared with patients with colon cancer, whereas permeability to dextran 40,000 was equal in the groups. Ovalbumin permeability was

Acknowledgements

The authors thank Lisbeth Hedman and Inger Matsson for excellent laboratory work.

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    Supported by grants from the County Council of Östergötland; “Förenade liv” Mutual Group Life Insurance Company, Stockholm; Swedish Society for Medical Research, Swedish Society of Medicine; and Swedish Medical Research Council (projects 05983 and 12618).

    ☆☆

    Address requests for reprints to: Johan D. Söderholm, M.D., Ph.D., Department of Surgery, University Hospital, S-581 85 Linköping, Sweden. e-mail: [email protected]; fax: (46) 13-22-35-70.

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