| Co-Investigator(Kenkyū-buntansha) |
SUGITOH Kiminobu Nihon University School of Medicine, Assistant Professor, 医学部, 助手 (10328750)
JI PARK Yeong Nihon University School of Medicine, Assistant Professor, 医学部, 助手 (70318426)
FUKUZAWA Masahiro Nihon University School of Medicine, Professor, 医学部, 教授 (60165272)
|
|---|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Research Abstract |
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.
|
