Increased epithelial uptake of protein antigens in the ileum of Crohn’s disease mediated by tumour necrosis factor α

• Published in: Gut 2004-12, Vol.53 (12), p.1817-1824
• Main Authors: Söderholm, J D, Streutker, C, Yang, P-C, Paterson, C, Singh, P K, McKay, D M, Sherman, P M, Croitoru, K, Perdue, M H
• Format: Article
• Language: English
• Subjects: Adult; Antigens - metabolism; Biological and medical sciences; Cell Line; Crohn Disease - metabolism; Crohn’s disease; Dose-Response Relationship, Drug; electron microscopy; endocytosis; Endosomes - metabolism; Female; GAPDH; Gastroenterology. Liver. Pancreas. Abdomen; glyceraldehyde-3-phosphate dehydrogenase; horseradish peroxidase; Horseradish Peroxidase - pharmacokinetics; HRP; Humans; Ileum - metabolism; Inflammatory Bowel Disease; Intestinal Mucosa - metabolism; Isc; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Other diseases. Semiology; Permeability; potential difference; reverse transcripion-polymerase chain reaction; RNA, Messenger - genetics; RT-PCR; short circuit current; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T84 cell line; TER; TNF-α; transepithelial electrical resistance; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - physiology; tumour necrosis factor α
• ISSN: 0017-5749; 1468-3288; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2004.041426

Background and aims: The exact nature of the epithelial barrier defect in Crohn’s disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn’s disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology. Methods: Macroscopically normal segments of distal ileum of Crohn’s disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor α (TNF-α) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-α on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports. Results: The area of horseradish peroxidase containing endosomes was increased (p