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

阻断粘膜寻址细胞粘附分子-1 (MAdCAM-1) 在大鼠小肠移植模型中的作用。

基本信息

批准号：
16591784
负责人：
HASEGAWA Toshimichi
金额：
$ 2.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

[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..

【目的】采用大鼠小肠移植模型，观察抗体阻断移植物粘膜寻址蛋白细胞粘附分子-1 （muc粘膜寻址蛋白细胞粘附分子-1，MAdCAM-1）表达的效果，以及移植物的免疫组织化学变化。【材料与方法】将DA大鼠小肠异位移植到Lewis大鼠体内。在手术过程中，移植物分别使用或不使用抗madcam -1抗体F(ab)2。观察移植物的存活情况和组织学变化，如淋巴细胞浸润和肠结构的破坏，观察移植物的上皮绒毛厚度、绒毛高度和粘膜下厚度。免疫染色法检测移植物中MAdCAM-1和β7整合素的表达。采用FACS法检测移植物浸润淋巴细胞、肠系膜淋巴结（MLN）和Peyer’s patches （PP）。[结果]抗MAdCAM-1 F(ab')2治疗可延长DA移植物的生存期；DA到LEW: 7.0±3.3天，DA到LEW带抗体：24.6±8.4天（p< 0.05）。移植物的组织学表现和评分与这一结果一致。此外，MAdCAM-1本身的表达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CD4+ T细胞和CD8+ T细胞的百分比没有差异，但抗体处理的移植物MLN中CD4+ T细胞的百分比明显低。[结论]阻断小肠移植物黏附分子MAdCAM-1的策略可能有助于预防小肠移植后的急性排斥反应。