Expression of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) During Small-Bowel Graft Rejection in Rats

Abstract

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 portacaval 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 μm 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.