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

背景资料。粘膜寻址蛋白细胞黏附分子-1(MAdCAM-1)是在生理条件下淋巴细胞向肠道相关淋巴组织(GaULT)转运的关键内皮细胞黏附分子，表达于GALT中特殊的毛细血管后小静脉(HEV)。在这项研究中，我们研究了MAdCAM-1在小肠移植排斥反应中的表达变化。采用原位小肠移植(SBT)联合门腔静脉引流的方法，从Brown挪威(BN)大鼠到Lewis(LEW)大鼠。同种异体移植(LEW→LEW)和未移植动物作为对照。分别于SBT后第3、4、5、6、7天处死动物。6 mm厚的冷冻切片取自正常的小肠组织和移植的小肠，包括Peyer‘s补片(PPS)。用抗大鼠MAdCAM-1(OST12)的单抗进行间接免疫过氧化物酶染色。在对照组的PPS中，MAdCAM-1抗体特异性地染色HEV的内皮细胞，这些细胞主要位于滤泡间区(IFA)。在SBT后第4天的同种异体移植中，PPS组HEV上MAdCAM-1的表达弱于对照组。在对照组固有层，MAdCAM-1在血管上有微弱表达。同种异体移植后第4天，MAdCAM-1在绒毛底部血管内皮细胞表达增强。随着排斥反应的发展，血管上MAdCAM-1的表达逐渐向绒毛末端发展。MAdCAM-1的表达变化可能参与了小肠移植排斥反应的发生。绒毛底部的血管与淋巴细胞募集有关，可能成为同种异体小肠移植排斥反应早期免疫反应强烈的部位。

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.