Effect of Blocking the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) in a Rat Small Intestinal Transplantation Model.

[目的]采用大鼠小肠移植模型，观察用抗体阻断移植物中粘膜地址素细胞粘附分子-1（MAdCAM-1）表达的效果，以及移植物中的免疫组织化学变化。[材料与方法]将黑琼脂（DA）大鼠小肠异位移植到刘易斯（LEW）大鼠体内。在手术过程中，用或不用抗MAdCAM-1抗体F（ab）2处理移植物。观察移植物存活情况及移植物上皮、绒毛厚度、绒毛高度、粘膜下厚度等组织学改变，如淋巴细胞浸润和肠结构破坏。免疫组化法检测移植物中MAdCAM-1和β7整合素的表达。此外，通过FACS分析测量肠系膜淋巴结（MLN）和派尔集合淋巴结（PP）中的移植物浸润淋巴细胞。[结果]抗MAdCAM-1F（ab '）2处理后DA移植物存活时间延长，DA移植物存活至LEW移植物存活时间为7.0 ± 3.3天，抗MAdCAM-1F（ab'）2处理后DA移植物存活至LEW移植物存活时间为24.6 ± 8.4天（p< 0.05）。移植物的组织学结果和评分与该结果一致。此外，MAdCAM-1表达本身在抗体处理组的移植物中被抑制。虽然FACS分析显示移植物PP中CD 4 + T细胞和CD 8 + T细胞的%没有差异，但抗体处理的移植物MLN中的CD 4 + T细胞显著低。[结论]阻断小肠移植物中粘附分子MAdCAM-1的表达可能有助于预防小肠移植术后急性排斥反应的发生。

[Puupose] The effect of blocking the expression of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in a graft by an antibody, and immunohistochemical changes in the graft were monitored, using a rat small intestinal transplantation model.[Materials and Methods] Dark Agouti (DA) rat small intestines were heterotopically transplanted into Lewis (LEW) rats. The graft was treated with or without anti-MAdCAM-1 antibody, F(ab)2, during the operation. The survival of the grafts and histological changes, such as lymphocyte infiltration and destruction of the intestinal architecture in the epithelium villus thickess, villus height and submucosal thickness of the graft were examined. The expression of MAdCAM-1 and β7 integrin in the graft was also checked by immunostaining. Furthermore, graft infiltration lymphocytes, in mesenteric lymph nodes (MLN) and Peyer's patches (PP) were measured by FACS analysis.[Results] Survival was prolonged in the DA graft with anti MAdCAM-1 F(ab')2 treatment; DA to LEW: 7.0 ± 3.3 days, DA to LEW with the antibody: 24.6 ± 8.4 days (p< 0.05). Histological findings and scoring of the grafts were consistent with this result. Moreover, MAdCAM-1 expression itself was suppressed in grafts of the antibody-treated group. While a FACS analysis showed no difference in the % of CD4+ T cells and CD8+ T cells in the PP of the graft, CD4+ T cells in the MLN of the antibody treated graft were significantly low.[Conclusion] A strategy directed at blocking the adhesion molecule, MAdCAM-1, in the small intestinal grafts could be useful in prevention of acute rejection after small intestinal transplantation..