Effect of combined treatment with FK506, FTY720, and ex vivo graft irradiation in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.
We studied the effect of the combined treatment with FK506, FTY720, and ex vivo graft irradiation. Five groups of SBT animals were studied on days 3, 5, and 7 after operation (untreated, FK506, FTY720, FK506 + FTY720, FK506 + FTY720 + irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The numbers of CD4 positive cells in allografts were also analyzed by flow cytometry. The graft survival was prolonged in all of the FK506- and FTY720-treated groups. SBT allografts treated by FK506 and FTY720 demonstrated less infiltration of CD4 positive cells, but the irradiation group did not show any effects on its expression. In FK506- and FTY720-treated groups, MAdCAM-1 expression on the HEVs in PPs was up-regulated, and its expression on the ECVs in the LP was down-regulated compared with other allograft groups. Irradiation did not show any effects on MAdCAM-1 expression on both HEVs in PPs and ECVs in LP. FK506 and FTY720 prevented the infiltration of CD4 positive cells, the down-regulation of MAdCAM-1 expression on HEVs in PPs, and the up-regulation of MAdCAM-1 expression on ECVs in LP during the early phase of SBT.
Sugito
Kiminobu
K
Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan. ksugito@med.nihon-u.ac.jp
Uekusa
Shota
S
Kawashima
Hiroyuki
H
Masuko
Takayuki
T
Furuya
Takeshi
T
Konuma
Noriyoshi
N
Ohashi
Kensuke
K
Inoue
Mikiya
M
Ikeda
Taro
T
Koshinaga
Tsugumichi
T
D000818:Animals; D003131:Combined Modality Therapy; D000068876:Fingolimod Hydrochloride; D007136:Immunoglobulins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects* / Q000637:transplantation; D009088:Mucoproteins / Q000096:biosynthesis*; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D019737:Transplants
D007136:Immunoglobulins; D007166:Immunosuppressive Agents; C504268:Madcam1 protein, rat; D009088:Mucoproteins; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D016559:Tacrolimus