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，观察抗体阻断移植物中粘膜寻址细胞黏附分子-1(MAdCAM-1)表达的效果及移植物免疫组织化学变化。术中应用或不使用抗MAdCAM-1抗体F(Ab)2处理移植物。观察移植物成活情况及移植肠上皮内淋巴细胞浸润、肠壁结构破坏、绒毛厚度、绒毛高度及粘膜下层厚度等组织学变化。免疫组织化学方法检测移植物中MAdCAM1和β7整合素的表达。[结果]抗MAdCAM-1 F(ab‘)2处理的DA移植物存活时间延长，DA to Lew为7.0±3.3天，DA为24.6±8.4 d(p&lt；0.05)。移植物的组织学发现和评分与这一结果一致。此外，抗体处理组的移植物中MAdCAM-1的表达本身也受到抑制。FACS分析显示移植物PP中的CD4+T细胞和CD8+T细胞的百分率无明显差异，而抗体处理的移植物MLN中的CD4+T细胞明显减少。[结论]针对移植物中黏附分子MAdCAM-1的阻断策略可有效地预防小肠移植后的急性排斥反应。

[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..