Knight R J, Dikman S, Liu H, Martinelli G P
Department of Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
Transplantation. 1997 Oct 27;64(8):1102-7. doi: 10.1097/00007890-199710270-00003.
The pathogenesis of chronic rejection likely involves an interplay between immunogenic and nonimmunogenic factors. The objective of this study was to determine the influence of cold ischemic preservation injury on the rate of progression to chronic rejection in the Lewis to F344 cardiac allograft model.
To induce an ischemic injury, donor hearts were stored for 3 hr at 4 degrees C in University of Wisconsin solution before transplantation. Allografts were excised at 1, 7, and 90 days after transplantation or at rejection. Vasculopathy was graded for degree of intimal thickening based on the involvement of vascular perimeter and luminal compromise.
The degree of vessel injury in ischemic injured allografts at 90 days was significantly greater than in nonischemic injured allografts (2.8+/-0.4 vs. 1.6+/-0.5, P<0.05). Ischemic injury in syngeneic grafts did not induce a vasculopathy. Immunoperoxidase staining with R73 (anti-T cell) and ED1 (anti-macrophage) monoclonal antibodies revealed that, in ischemic injured allografts at 90 days after transplantation, the infiltrate was composed predominantly of T cells and macrophages. Additionally, ischemic injured allografts excised at 7 days after transplantation showed cellular infiltrates composed of R73-positive T cells and rare interleukin-2 receptor-positive cells, which was not observed in nonischemic allografts or ischemic syngeneic grafts.
The progression to chronic vasculopathy in this model is principally an immunologic process, which is accelerated by an ischemic insult to the allograft. The vascular injury is mediated in part by T cells and macrophages.
慢性排斥反应的发病机制可能涉及免疫原性和非免疫原性因素之间的相互作用。本研究的目的是确定在Lewis到F344心脏移植模型中，冷缺血保存损伤对慢性排斥反应进展速率的影响。
为诱导缺血性损伤，供体心脏在移植前于4℃用威斯康星大学溶液保存3小时。在移植后1天、7天和90天或排斥反应时切除移植心脏。根据血管周长受累情况和管腔狭窄程度对血管病变的内膜增厚程度进行分级。
90天时，缺血损伤移植心脏的血管损伤程度显著高于非缺血损伤移植心脏（2.8±0.4对1.6±0.5，P<0.05）。同基因移植中的缺血损伤未诱导血管病变。用R73（抗T细胞）和ED1（抗巨噬细胞）单克隆抗体进行免疫过氧化物酶染色显示，在移植后90天的缺血损伤移植心脏中，浸润细胞主要由T细胞和巨噬细胞组成。此外，移植后7天切除的缺血损伤移植心脏显示由R73阳性T细胞和罕见的白细胞介素-2受体阳性细胞组成的细胞浸润，在非缺血移植心脏或缺血同基因移植心脏中未观察到这种情况。
在该模型中，慢性血管病变的进展主要是一个免疫过程，同种异体移植的缺血性损伤会加速这一过程。血管损伤部分由T细胞和巨噬细胞介导。
