Volume 116, Issue 2, Pages 301-309 (February 1999) Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis Heinz Schmitz*, Christian Barmeyer*, MichaeL Fromm‡, Norbert Runkel§, Hans-Dieter Foss∥, Carl J. Bentzel¶, Ernst-Otto Riecken*, Jörg-Dieter Schulzke* Gastroenterology Volume 116, Issue 2, Pages 301-309 (February 1999) DOI: 10.1016/S0016-5085(99)70126-5 Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 1 Original impedance locus plots of human colon. (A) Control; (B) UC. Zreal is the ohmic component, and Zimaginary is the reactive component of the complex impedance. Intersections between the semicircle and x-axis at low and high frequencies represent Rt and Rsub, respectively. Rt − Rsub = Re. For a detailed explanation of transepithelial impedance data, see Gitter et al.25 and Schulzke et al.26 Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 2 Conventional histology from colectomy specimens. (A) Control sigmoid colon; (B) sigmoid colon from patients with UC (original magnification 53×). Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 2 Conventional histology from colectomy specimens. (A) Control sigmoid colon; (B) sigmoid colon from patients with UC (original magnification 53×). Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 3 Freeze-fracture EM from the TJ region of colonic enterocytes. (A) Control; (B) UC. Bar = 200 nm; mv, microvilli; tj, TJ strands. (C) Pictorial drawing of strands in a TJ as seen by freeze-fracture EM. Vertical grid lines (counting lines) were drawn perpendicular to the most luminal strand at 83-nm intervals on electron micrographs (original magnification 60,000×). Parameters for morphometrical analysis consist of the number of strands within the main compact meshwork of the TJ (strand number) as well as the total depth of the TJ (total depth) and the depth of the main compact meshwork (meshwork depth). Strand discontinuities were also analyzed. Note that the aberrant strand below the main compact meshwork is transsected by the vertical grid line but is not counted. The total number of grid lines drawn and analyzed is important because it reflects the longitudinal extent of TJ analyzed. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 3 Freeze-fracture EM from the TJ region of colonic enterocytes. (A) Control; (B) UC. Bar = 200 nm; mv, microvilli; tj, TJ strands. (C) Pictorial drawing of strands in a TJ as seen by freeze-fracture EM. Vertical grid lines (counting lines) were drawn perpendicular to the most luminal strand at 83-nm intervals on electron micrographs (original magnification 60,000×). Parameters for morphometrical analysis consist of the number of strands within the main compact meshwork of the TJ (strand number) as well as the total depth of the TJ (total depth) and the depth of the main compact meshwork (meshwork depth). Strand discontinuities were also analyzed. Note that the aberrant strand below the main compact meshwork is transsected by the vertical grid line but is not counted. The total number of grid lines drawn and analyzed is important because it reflects the longitudinal extent of TJ analyzed. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 3 Freeze-fracture EM from the TJ region of colonic enterocytes. (A) Control; (B) UC. Bar = 200 nm; mv, microvilli; tj, TJ strands. (C) Pictorial drawing of strands in a TJ as seen by freeze-fracture EM. Vertical grid lines (counting lines) were drawn perpendicular to the most luminal strand at 83-nm intervals on electron micrographs (original magnification 60,000×). Parameters for morphometrical analysis consist of the number of strands within the main compact meshwork of the TJ (strand number) as well as the total depth of the TJ (total depth) and the depth of the main compact meshwork (meshwork depth). Strand discontinuities were also analyzed. Note that the aberrant strand below the main compact meshwork is transsected by the vertical grid line but is not counted. The total number of grid lines drawn and analyzed is important because it reflects the longitudinal extent of TJ analyzed. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 4 Distribution of the number of horizontally oriented strands along the TJ of colonic enterocytes under control conditions (▩) and in UC (■). Values represent the percentage of grid lines with the respective strand count (related to the total number of grid lines analyzed). Specifically, this represents 208 × 83 nm of TJ analyzed from 9 control patients and 395 × 83 nm of TJ analyzed from 9 patients with UC. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 5 Electrogenic Cl− secretory system in UC. ΔISC as a function of chloride concentration in the bathing medium. Tissues are stimulated by 0.1 μmol/L carbachol, 10 μmol/L PGE1, and 10 μmol/L theophylline to characterize their maximal transport capacity. Data are given as (A) rough data and (B) corrected for Rsub contributions. (C) Eadie–Hofstee plot of the data in B. After correction for the Rsub, the calculated maximum ΔISC (ΔIscmax) was 1.80 ± 0.48 μmol · h−1 · cm−2 (n = 6) in control and 1.17 ± 0.28 μmol · h−1 · cm−2 (n = 5; P = NS) in UC. Km was 13 ± 4 mmol/L in control and 16 ± 6 mmol/L (NS) in UC. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 5 Electrogenic Cl− secretory system in UC. ΔISC as a function of chloride concentration in the bathing medium. Tissues are stimulated by 0.1 μmol/L carbachol, 10 μmol/L PGE1, and 10 μmol/L theophylline to characterize their maximal transport capacity. Data are given as (A) rough data and (B) corrected for Rsub contributions. (C) Eadie–Hofstee plot of the data in B. After correction for the Rsub, the calculated maximum ΔISC (ΔIscmax) was 1.80 ± 0.48 μmol · h−1 · cm−2 (n = 6) in control and 1.17 ± 0.28 μmol · h−1 · cm−2 (n = 5; P = NS) in UC. Km was 13 ± 4 mmol/L in control and 16 ± 6 mmol/L (NS) in UC. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions
Fig. 5 Electrogenic Cl− secretory system in UC. ΔISC as a function of chloride concentration in the bathing medium. Tissues are stimulated by 0.1 μmol/L carbachol, 10 μmol/L PGE1, and 10 μmol/L theophylline to characterize their maximal transport capacity. Data are given as (A) rough data and (B) corrected for Rsub contributions. (C) Eadie–Hofstee plot of the data in B. After correction for the Rsub, the calculated maximum ΔISC (ΔIscmax) was 1.80 ± 0.48 μmol · h−1 · cm−2 (n = 6) in control and 1.17 ± 0.28 μmol · h−1 · cm−2 (n = 5; P = NS) in UC. Km was 13 ± 4 mmol/L in control and 16 ± 6 mmol/L (NS) in UC. Gastroenterology 1999 116, 301-309DOI: (10.1016/S0016-5085(99)70126-5) Copyright © 1999 American Gastroenterological Association Terms and Conditions