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Updated: Aug 8, 2026
Orthotopic Small Bowel Transplantation in Rats
Published on: November 6, 2012
Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) during small-bowel graft rejection in rats
S Fujisaki1, Y J Park, Y Kimizuka
1First Dept. of Surgery, Nihon University School of Medicine, Tokyo, Japan. sfujisak@med.nihon-u.ac.jp
Insights
Changes in mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression are linked to small-bowel graft rejection. Increased MAdCAM-1 on villus base vessels suggests early immune activity in rejection.
Area of Science:
- Immunology
- Transplantation Biology
- Gastroenterology
Background:
- Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is crucial for lymphocyte homing to gut-associated lymphoid tissues (GALT).
- MAdCAM-1 is typically expressed on high endothelial venules (HEVs) within GALT.
- This study examines MAdCAM-1 expression dynamics during small-bowel graft rejection.
Purpose of the Study:
- To investigate alterations in MAdCAM-1 expression during small-bowel allograft rejection.
- To identify specific vascular sites involved in immune cell recruitment during rejection.
Main Methods:
- Orthotopic small-bowel transplantation (SBT) performed in a rat model (Lewis rats receiving grafts from Brown Norway rats).
- Control groups included isografts and untransplanted animals.
- Immunohistochemical staining for MAdCAM-1 on small-bowel tissues and grafts at various time points post-SBT.
Main Results:
- MAdCAM-1 was localized to HEVs in Peyer's patches (PPs) of control animals.
- A decrease in MAdCAM-1 expression on PP HEVs was observed on day 4 post-SBT in allografts.
- Upregulation of MAdCAM-1 was noted on vessels at the villus base in allografts by day 4, progressing towards the villus tip as rejection advanced.
Conclusions:
- Altered MAdCAM-1 expression patterns correlate with the development of small-bowel graft rejection.
- Vessels at the base of the villi emerge as a key site for lymphocyte recruitment and immune reactivity in early allograft rejection.
Background:
Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a critical endothelial adhesion molecule for lymphocyte trafficking to gut-associated lymphoid tissues (GALT) under physiological conditions. It is expressed on special postcapillary venules, that is the high endothelial venules (HEV) in GALT. In this study, we investigated changes in MAdCAM-1 expression during small-bowel graft rejection.
Methods:
Orthotopic small-bowel transplantation (SBT) with portocaval drainage was performed from brown Norway (BN) rats to Lewis (LEW) rats. Isografted (LEW --> LEW) and untransplanted animals served as controls. Animals were killed on days 3, 4, 5, 6 and 7 after SBT. Cryostat sections (6 microm thick) were prepared from normal small-bowel tissues and small-bowel grafts, including Peyer patches (PPs). Indirect immunoperoxidase staining was performed using monoclonal antibodies (mAbs) against rat MAdCAM-1 (OST12).
Results:
In the PPs of controls, MAdCAM-1 antibodies specifically stained the endothelial cells of HEV, which were predominantly located in the interfollicular areas. In the allografts on day 4 after SBT, the MAdCAM-1 expression was weaker on the HEV in the PPs than in the controls. In the lamina propria of controls, a faint expression of MAdCAM-1 on vessels was observed. On day 4 after allogeneic SBT, the MAdCAM-1 was more strongly expressed on the endothelial cells of the vessels at the base of the villi. As rejection developed, the MAdCAM-1 expression on the vessels progressed toward the villus tip.
Conclusions:
The change of MAdCAM-1 expression may be involved in the development of small-bowel graft rejection. The vessels at the base of villi, which is associated with lymphocyte recruitment, may become a site of intense immune reactivity in the early phase of small-bowel allograft rejection.
