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

背景粘蛋白地址素细胞粘附分子-1（MAdCAM-1）是一种重要的内皮粘附分子，在生理条件下淋巴细胞向肠相关淋巴组织（GALT）运输过程中起重要作用，表达于GALT特殊的毛细血管后微静脉，即高内皮微静脉。在这项研究中，我们研究了MAdCAM-1表达的变化在小肠移植排斥反应。采用门腔静脉置管引流的方法，对Brown Norway（BN）大鼠和刘易斯（LEW）大鼠进行原位小肠移植（SBT）。同系移植（LEW→LEW）和未移植动物作为对照。在SBT后第3、4、5、6和7天处死动物。从正常小肠组织和小肠移植物（包括派尔集合淋巴结（PP））制备6 mm厚的低温恒温切片。用抗大鼠MAdCAM-1（OST 12）单克隆抗体（mAb）进行间接免疫过氧化物酶染色。在对照的PP中，MAdCAM-1抗体特异性染色主要位于滤泡间区（IFA）的HEV内皮细胞。在SBT后第4天的同种异体移植物中，PP中HEV上的MAdCAM-1表达弱于对照。在对照组的固有层中，观察到MAdCAM-1在血管上的微弱表达。在同种异体SBT后第4天，MAdCAM-1在绒毛基部的血管内皮细胞上表达更强。随着排斥反应的发展，MAdCAM-1在血管上的表达逐渐向绒毛尖端发展。MAdCAM-1表达的改变可能参与了小肠移植排斥反应的发生。小肠绒毛底部的血管与淋巴细胞募集有关，在小肠移植排斥反应的早期阶段可能成为强烈免疫反应的部位。

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.