Influence of mast cells on outcome after heterotopic cardiac transplantation in rats

Marjan Boerma, William P. Fiser, Grant Hoyt, Gerald J. Berry, Lija Joseph, Jacob Joseph, Junru Wang, Mark D. Crew, Robert C. Robbins, Martin Hauer-Jensen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Correlative data suggest that mast cells adversely affect cardiac transplantation. This study uses a mast cell-deficient rat model to directly address the role of mast cells in cardiac allotransplantation. Standardized cardiac heterotopic transplantation with cyclosporine immunosuppression was performed in mast cell-deficient and mast cell-competent rats. Rejection, ischemia, fibrosis, fibrin deposition, numbers of T-cell receptor α/β positive cells, expression of transforming growth factor-β (TGF-β), and of endothelin-1 (ET-1) and its receptors ETA and ETB were assessed. Differences in baseline cardiac gene expression were quantified by real-time PCR in a separate group of untransplanted animals. Baseline cardiac gene expression levels of all investigated growth factors, cytokines, ET-1, ETA, and ETB were similar in mast cell-deficient and mast cell-competent rats. Surprisingly, upon heterotopic transplantation, donor heart survival was significantly reduced in mast cell-deficient rats. Moreover, in mast cell-deficient donor hearts rejection was more severe, although nonsignificant, and extracellular matrix associated TGF-β immunoreactivity was significantly lower than in mast cell-competent donor hearts. Fibrin immunoreactive area, on the other hand, was only increased in mast cell-deficient donor hearts, but not in mast cell-competent donor hearts. Histopathological changes in all donor hearts were accompanied by increased immunoreactivity for ET-1. In conclusion, this study shows that mast cells play a protective role after cardiac transplantation.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalTransplant International
Volume20
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Keywords

  • Animal models
  • Cardiac transplantation
  • Graft survival
  • Mast cells

ASJC Scopus subject areas

  • Transplantation

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