Effect of FTY720 and Ex Vivo Graft Irradiation in Rat Small Bowel Transplantation: Expression of Mucosal Addressin Cell Adhesion Molecule-1

• Published in: Surgery today (Tokyo, Japan) Vol. 38; no. 1; pp. 38 - 41
• Main Authors: Sugito, Kiminobu, Inoue, Mikiya, Ikeda, Taro, Hagiwara, Noritsugu, Koshinaga, Tsugumichi, Kusafuka, Takeshi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer-Verlag 2008
• Subjects: Animals; Cell Adhesion Molecules - biosynthesis; Disease Models, Animal; Fingolimod Hydrochloride; Graft Rejection - drug therapy; Graft Rejection - metabolism; Graft Rejection - radiotherapy; Graft Survival - drug effects; Graft Survival - radiation effects; Immunosuppressive Agents - therapeutic use; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - radiation effects; Intestine, Small - metabolism; Intestine, Small - radiation effects; Intestine, Small - transplantation; Medicine; Medicine & Public Health; Organ Transplantation - methods; Original Articles; Propylene Glycols - therapeutic use; Rats; Rats, Inbred BN; Rats, Inbred Lew; Sphingosine - analogs & derivatives; Sphingosine - therapeutic use; Surgery; Surgical Oncology; Transplantation, Homologous; MAdCAM-1; Small bowel transplantation; Ex vivo graft irradiation; FTY720
• ISSN: 0941-1291; 1436-2813
• DOI: 10.1007/s00595-007-3583-8

Purpose We performed a semiquantitative analysis of the expression of Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and gut-associated tissues (GALT) during small bowel graft rejection in the rat to confirm the effect of FTY720 and ex vivo graft irradiation. Methods Small bowel transplantations (SBT) were performed from BN rats to LEW rats. Four groups of SBT animals were studied on days 3, 5, and 7 after operations (untreated, FTY720, ex vivo graft irradiation, FTY720+ex vivo graft irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The number of CD4-positive cells in the allografts was also analyzed by flow cytometry. Results The graft survival was prolonged only in the FTY720-treated groups. The SBT allografts treated by FTY720 demonstrated less infiltration, but the ex vivo graft irradiation group did not show any effect on its expression. In the FTY720-treated groups, MAdCAM-1 expression on high endothelial venules (HEVs) in Peyer's patches (PPs) was upregulated and its expression on endothelial cells of vessels in the lamina propria was downregulated in comparison with the allograft group without FTY720. Conclusions It is important to prevent the infiltration of CD4-positive cells, the downregulation of MAdCAM-1 expression on HEVs in PPs and the upregulation of MAdCAM-1 expression on endothelial cells of vessels in the lamina propria for the prolongation of graft survival.