Bombesin can minimize impairments of interstitial cells of Cajal induced by FK506 in small bowel transplantation.
OBJECTIVE
Interstitial cells of Cajal (ICC) are known as intestinal pacemaker cells and express c-kit on their membrane. Previously, we reported that FK506 had neurotoxicity to enteric ganglia, and bombesin (BBS) preserved them against FK506. The aim of this study was to investigate whether ICC was impaired by FK506 and whether ICC was preserved by BBS against FK506.


METHODS
Twelve rats underwent allogeneic SBTx heterotopically and were divided into 2 groups as follows: group A underwent SBTx with FK506 and group B with FK506/BBS. All rats were administered FK506 daily. Either BBS or normal saline was infused continuously from day 14 to 28. Analysis of ICC was performed immunohistochemically with c-kit. Interstitial cells of Cajal were evaluated by counting the number of c-kit-positive clusters in each graft.


RESULTS
The expression of c-kit accumulated around 60% of PGP9.5-positive enteric ganglia. The number of c-kit-positive clusters in group A was 22.3 +/- 5.5 clusters per cross section (C/CS) and that in group B was 36.3 +/- 5.1 C/CS. Interstitial cells of Cajal were well preserved in group B. There was a significant difference between groups A and B (P <.001).


CONCLUSIONS
Interstitial cells of Cajal were impaired by FK506 in allografts, and BBS could minimize the impairment of ICC against FK506.
Higuchi
Koji
K
Department of Pediatric Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Kimura
Osamu
O
Furukawa
Taizo
T
Kinoshita
Hiromi
H
Iwai
Naomi
N
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006084:Graft Rejection / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous / Q000473:pathology
D007166:Immunosuppressive Agents; D018377:Neurotransmitter Agents; D019009:Proto-Oncogene Proteins c-kit; D001839:Bombesin; D016559:Tacrolimus