Effect of FTY720 and ex vivo graft irradiation in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.
OBJECTIVE
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.
Sugito
Kiminobu
K
Division of Pediatric Surgery, Department of Surgery, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
Inoue
Mikiya
M
Ikeda
Taro
T
Hagiwara
Noritsugu
N
Koshinaga
Tsugumichi
T
Kusafuka
Takeshi
T
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D007421:Intestine, Small / Q000378:metabolism / Q000528:radiation effects / Q000637:transplantation*; D009088:Mucoproteins; D016377:Organ Transplantation / Q000379:methods*; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous
D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine