title: Influence of mast cells on outcome after heterotopic cardiac transplantation in rats.
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 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.
authors.affiliation: Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA. mboerma@uams.edu
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
authors.forename: William P
authors.initials: WP
authors.lastname: Fiser
authors.forename: Grant
authors.initials: G
authors.lastname: Hoyt
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Berry
authors.forename: Lija
authors.initials: L
authors.lastname: Joseph
authors.forename: Jacob
authors.initials: J
authors.lastname: Joseph
authors.forename: Junru
authors.initials: J
authors.lastname: Wang
authors.forename: Mark D
authors.initials: MD
authors.lastname: Crew
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: 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
chemical_list: D016207:Cytokines