EXPRESSION OF MUCOSAL ADDRESSIN CELL ADHESION MOLECULE- (MAdCAM-1) DURING SMALL BOWEL GRAFT REJECTION IN RATS

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Background. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a critical endothelial adhesion molecule for lymphocyte trafficking to gut-associated lymphoid tissues (GAULT) under physiological conditions and it is expressed on special postcapillary venules, the high endothelial venules (HEV) in GALT. In this study, we investigated changes of 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 control. Animals were killed on days 3, 4, 5, 6 and 7 after SBT. Six-mm-thick cryostat sections were prepared from normal small bowel tissues and small bowel grafts, including Peyer's 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 (IFA). In the allografts on day 4 after SBT, the MAdCAM-1 expression was weaker on the HEV in the PPs than controls. In the lamina propria of controls, the 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 on the early phase of small bowel allograft rejection.