Mechanisms of chronic injury in a model of heart allograft chronic rejection / 中国免疫学杂志

ABSTRACT

Objective:To study the mechanisms of chronic injury in heart allograft with chronic rejection.Methods:A model of cardiac chronic rejection in the rat based on tolerance induced through donor specific blood transfusions was used.The subpopulation and the distribution of infiltrating cells and the expression of adhesion molecule and growth factors were studied by immunohistochemistry and Northern blot analysis in the chronic rejection model.Results:Infiltrating cells were predominantly T lymphocytes and macrophages,mostly evident in the interstitial,subendocardial and perivascular areas.Allografts were demonstrated significantly elevated number of CD45+,CD4+,CD8+,TCR+,CD45RB+ cells,macrophages(ED_1) and NK cells at both 3 and 6 months compared with normal rat hearts and isografts at 3 months.Damaged areas also were observed expression of the adhesion molecules ICAM-1,LFA-1,basic fibroblast growth factor (bFGF) and transforming growth factor(TGF-?1).Northern blot analysis of total RNA,showed 5 to 6 fold upregulation of TGF-?1 mRNA in the chronic rejection model compared with normal rat hearts.Conclusion:These results suggest that T lymphocytes and macrophages play a central role in the development on chronic rejection and the increased expression of ICAM-1,LFA-1,bFGF and TGF-?1 in this model supports the involvement of these adhesion molecules and growth factors in the development of cardiac allograft vasculopaphy.