Effect of Blocking the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) in a Rat Small Intestinal Transplantation Model.
| Project/Area Number |
16591784
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Osaka University |
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Principal Investigator |
HASEGAWA Toshimichi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20294085)
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| Co-Investigator(Kenkyū-buntansha) |
WASA Masafumi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10240467)
FUKUZAWA Masahiro Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (60165272)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | small intestinal transplantation / immunosuppression / inhibition of costimulation molecule / adhesion molecule / lymphocyte homing / anti-MAdCAM-1 antibody / 拒絶反応 / 抗ICOS抗体 |
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| Research Abstract |
[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..
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Report
(3 results)
Research Products
(2 results)
