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- Waltenberger, J., et al.
(författare)
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Induction of transforming growth factor-beta during cardiac allograft rejection
- 1993
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Ingår i: J Immunol. ; 151:2, s. 1147-57
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Tidskriftsartikel (refereegranskat)abstract
- The polypeptides of the transforming growth factor-beta (TGF-beta) family are potent endogenous immuno-regulators. Using a rat cardiac allograft transplant model, we investigated the expression of the precursor forms of TGF-beta 1, TGF-beta 2, and TGF-beta 3 and the latent TGF-beta binding protein (LTBP) by immunohistochemistry. The activity of TGF-beta in the extracts from transplanted as well as normal hearts was measured using a bioassay, and Northern blot analysis was performed on RNA extracts. The transplanted hearts were analyzed both during acute rejection up to 6 days and during chronic rejection up to 6 mo after transplantation and compared with normal controls. The animals of the chronic rejection group received cyclosporin A for immunosuppression. The TGF-beta bioactivity dramatically increased in the transplanted allografts during the chronic rejection process compared to the normal hearts, and so did the immunostaining as well as the mRNA levels for TGF-beta 1 and, to a lesser extent, the immunostaining for TGF-beta 2. TGF-beta 3 expression remained unchanged and was only found in the myocardium in trace amounts. During the acute rejection process up to 6 days after transplantation, TGF-beta immunoreactivity increased only slightly, whereas the TGF-beta mRNA was severalfold increased. Control animals treated with cyclosporin A showed a similar pattern at day 6 with regard to TGF-beta expression. LTBP was induced simultaneously with TGF-beta 1 and occurred within interstitial spaces of the myocardium. The TGF-beta was produced by macrophage-like infiltrating lymphocytes. In conclusion, highly elevated levels of TGF-beta and LTBP were found during chronic rejection of cardiac allografts in rats. The induction of TGF-beta may counteract the rejection process and could be useful for new therapeutic approaches in the prevention of allograft rejection.
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| 4. |
- Wanders, A., et al.
(författare)
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Presence of polymorphonuclear granulocytes during the early stage of transplant arteriosclerosis after prolonged ischemia in the rat
- 1994
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Ingår i: Transpl Int. ; 7 Suppl 1, s. S371-5
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Tidskriftsartikel (refereegranskat)abstract
- The presence and function of polymorphonuclear granulocytes has been investigated, in particular, in the microcirculation in many short-term models of ischaemia/reperfusion injury. The aim of this study was to examine the presence of granulocytes in the aorta in a recently established long-term model of transplant arteriosclerosis, based on prolonged cold graft ischaemia time in the rat. Aortic grafts of PVG donors were subjected to two different cold ischaemia times of 1 and 4 h (n = 5 in each group) before an orthotopic transplantation to syngeneic recipients. The grafts were explanted shortly after various times post-reperfusion (7.5 min 24 h) and examined with conventional staining, immunohistochemistry and transmission electron microscopy for the presence of granulocytes. The results showed the presence of these cells adherent to the endothelial layer or in the subendothelial layer in grafts with both ischaemia times and with a maximum seen 2 h after transplantation. The internal elastic lamina was interrupted at sites of granulocyte adherence. We concluded that the polymorphonuclear granulocyte may be involved in the ischaemia/reperfusion injury in this model, thus, contributing to the development of accelerated transplant arteriosclerosis.
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