Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1759-1764
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1759
Beta-7 integrin controls enterocyte migration in the small intestine
Elke Kaemmerer, Paula Kuhn, Ursula Schneider, Thomas Clahsen, Min Kyung Jeon, Christina Klaus, Julia Andruszkow, Michael Härer, Sabine Ernst, Angela Schippers, Norbert Wagner, Nikolaus Gassler
Elke Kaemmerer, Paula Kuhn, Ursula Schneider, Min Kyung Jeon, Christina Klaus, Julia Andruszkow, Michael Härer, Nikolaus Gassler, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
Elke Kaemmerer, Thomas Clahsen, Angela Schippers, Norbert Wagner, Department of Pediatrics, RWTH Aachen University, 52074 Aachen, Germany
Sabine Ernst, Department of Medical Statistics, RWTH Aachen University, 52074 Aachen, Germany
Author contributions: Kaemmerer E, Klaus C and Gassler N designed the research; Kaemmerer E, Kuhn P, Schneider U, Clahsen T and Jeon M performed the research; Andruszkow J, Härer M and Ernst S contributed analytic tools; Kaemmerer E, Clahsen T, Klaus C, Schippers A, Wagner N and Gassler N wrote the paper; Kaemmerer E and Kuhn P contributed equally.
Supported by Partially by Deutsche Forschungsgemeinschaft, DFG GA 785/5-1 and Deutsche Krebshilfe, GA 109313.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nikolaus Gassler, Professor, Institute of Pathology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany. ngassler@ukaachen.de
Telephone: +49-241-8088897 Fax: +49-241-8082439
Received: May 22, 2014
Peer-review started: May 22, 2014
First decision: June 10, 2014
Revised: July 8, 2014
Accepted: July 24, 2014
Article in press: July 25, 2014
Published online: February 14, 2015
Processing time: 265 Days and 17.4 Hours
Abstract

AIM: To hypothesize that beta-7 integrin affects cellular migration of both, lymphocytes and enterocytes.

METHODS: The nucleoside analog BrdU was ip injected in beta-7-deficient mice (C57BL/6-Itgbtmlcgn/J) of male gender and age-matched male C57BL/J J mice (wild type) 4, 20, or 40 h before analysis. The total small intestine was isolated, dissected, and used for morphometrical studies. BrdU-positive epithelial cells were numbered in at least 15 hemi-crypts per duodenum, jejunum, and ileum of each animal. The outer most BrdU-positive cell (cellmax) was determined per hemi-crypt, numerically documented, and statistically analysed.

RESULTS: Integrins containing the beta-7-chain were exclusively expressed on leukocytes. In the small intestinal mucosa of beta-7 integrin-deficient mice the number of intraepithelial lymphocytes was drastically decreased. Moreover, the Peyer’s patches of beta-7 integrin-deficient mice appeared hypoplastic. In beta-7 integrin-deficient mice the location of cellmax was found in a higher position than it was the case for the controls. The difference was already detected at 4 h after BrdU application, but significantly increased with time (40 h after BrdU injection) in all small intestinal segments investigated, i.e., duodenum, jejunum, and ileum. Migration of small intestinal enterocytes was different between the experimental groups measured by cellmax locations.

CONCLUSION: The E-cadherin beta-7 integrin pathway probably controls migration of enterocytes within the small intestinal surface lining epithelial layer.

Keywords: Barrier function; Cell migration; Inflammatory bowel disease; Integrin; Intercellular junctions

Core tip: Integrins are involved in migration of epithelial and non-epithelial cells. beta-7-chain integrins are exclusively expressed on leukocytes and important for homing of lymphocytes into the intestinal mucosa. In beta-7 integrin-deficient mice, the number of intraepithelial lymphocytes is drastically decreased and accompanied by a significant increase in enterocyte migration along the crypt-villus axis. This phenomenon is probably mediated by the E-cadherin beta-7 integrin pathway.