Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?
OBJECTIVE
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.
Söderholm
J D
JD
Department of Surgery and Clinical Research Center, University Hospital, Linköping, Sweden. Johan.D.Soderholm@mtk.us.lio.se
Peterson
K H
KH
Olaison
G
G
Franzén
L E
LE
Weström
B
B
Magnusson
K E
KE
Sjödahl
R
R
D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism* / Q000503:physiopathology; D003911:Dextrans / Q000493:pharmacokinetics; D004492:Edetic Acid / Q000493:pharmacokinetics; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010047:Ovalbumin / Q000493:pharmacokinetics; D010539:Permeability
D003911:Dextrans; D046911:Macromolecular Substances; D010047:Ovalbumin; D004492:Edetic Acid