Bombesin can minimize impairments of interstitial cells of Cajal induced by FK506 in small bowel transplantation

J Pediatr Surg. 2009 Mar;44(3):541-5. doi: 10.1016/j.jpedsurg.2008.06.044.

Abstract

Purpose: 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).

Conclusion: Interstitial cells of Cajal were impaired by FK506 in allografts, and BBS could minimize the impairment of ICC against FK506.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombesin / pharmacology*
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology
  • Graft Rejection / prevention & control
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • Intestinal Mucosa / pathology
  • Intestine, Small / cytology
  • Intestine, Small / metabolism
  • Intestine, Small / transplantation*
  • Male
  • Neurotransmitter Agents / pharmacology*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Tacrolimus / pharmacology*
  • Transplantation, Homologous / pathology

Substances

  • Immunosuppressive Agents
  • Neurotransmitter Agents
  • Proto-Oncogene Proteins c-kit
  • Bombesin
  • Tacrolimus