Influence of mast cells on outcome after heterotopic cardiac transplantation in rats.
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 alpha/beta positive cells, expression of transforming growth factor-beta (TGF-beta), 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-beta 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.
Boerma
Marjan
M
Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA. mboerma@uams.edu
Fiser
William P
WP
Hoyt
Grant
G
Berry
Gerald J
GJ
Joseph
Lija
L
Joseph
Jacob
J
Wang
Junru
J
Crew
Mark D
MD
Robbins
Robert C
RC
Hauer-Jensen
Martin
M
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D006085:Graft Survival / Q000502:physiology; D016027:Heart Transplantation / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D016042:Transplantation, Heterotopic / Q000276:immunology
D016207:Cytokines