Volume 117, Issue 1, Pages 65-72 (July 1999) Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?  Johan D. Söderholm*, Kajsa Holmgren Peterson‡, Gunnar Olaison*, Lennart E. Franzén§, Björn Weström∥, Karl-Eric Magnusson‡, Rune Sjödahl*  Gastroenterology  Volume 117, Issue 1, Pages 65-72 (July 1999) DOI: 10.1016/S0016-5085(99)70551-2 Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 1 Cumulative transmucosal permeation of ovalbumin in human ileal mucosa in vitro in Ussing chambers. Specimens from noninflamed ileal mucosa from CD patients (■; n = 5) and ileal mucosa from colon cancer patients (○; n = 7). Symbols indicate median (25th–75th interquartile range) of cumulative passage of ovalbumin at each time point during the 90 minutes of the experiments. Note difference in lag phase for transmucosal permeation between the noninflamed CD specimens and colon cancer specimens. Ovalbumin permeation was higher in the noninflamed mucosa from CD patients at all time points from 20 to 90 minutes. Gastroenterology 1999 117, 65-72DOI: (10.1016/S0016-5085(99)70551-2) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 2 High-magnification CLSM of two epithelial cells in a human ileal villus; cell boundaries are outlined in C. Dual labeling was done with Texas Red–ovalbumin (red) and FITC–dextran 40,000 (green). Red and green together stains yellow. Bars = 2 μm. (A) Red labeling of the cytoplasm, but no labeling of the nuclei. Moreover, there is a patchy distribution of stronger stained areas in the periphery of the cells. This suggests both intracellular and paracellular uptake of ovalbumin-related peptides. (B) Green labeling was found only in the periphery of the cells, suggesting a dominance of paracellular uptake of dextran 40,000. (C) Summation of A and B, showing the red (ovalbumin and related peptides) dominance intracellularly and the yellow (dextran + ovalbumin and peptides) patchy pattern in the paracellular spaces. White lines show epithelial cell boundaries. Gastroenterology 1999 117, 65-72DOI: (10.1016/S0016-5085(99)70551-2) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 Confocal sectioning of human ileal mucosa at the (A–C) apical and (D–F) intermediate parts of a villus and (G–I) in the crypt region. (A, D, and G) Absorption pattern for ovalbumin and related peptides (Texas Red); (B, E, and H) pattern for FITC–dextran 40,000 (green); and (C, F, and I) summation of both probes (red and green together stains yellow). Bars = 10 μm. (A, B, and C) Section from the apical part of a villus, showing (A) uptake of ovalbumin and related peptides throughout the epithelium (red) and (B) patchy uptake of dextran in a paracellular pattern (green). (C) Summation of the probes shows patchy colocalization of ovalbumin and related peptides and dextran (yellow). The cells in the lamina propria stain both red and yellow, which could imply uptake of both marker molecules into the immunoreactive cells in the lamina propria after epithelial passage. (D, E, and F) CLSM section through the intermediate part of three villi. Red staining was seen throughout the epithelium, but weaker than in the apical section (D), and a patchy green staining with a paracellular pattern was found (E). (F) Paracellular colocalization of ovalbumin and related peptides and dextran was also seen. Thus the absorption patterns were the same as in the apex. (G, H, and I) Sectioning through a crypt area. The staining is weak, but similar differences in uptake patterns between ovalbumin and related peptides and dextran were seen also in this region. Gastroenterology 1999 117, 65-72DOI: (10.1016/S0016-5085(99)70551-2) Copyright © 1999 American Gastroenterological Association Terms and Conditions