Adams D H, Wyner L R, Karnovsky M J
Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Transplantation. 1993 Oct;56(4):794-9. doi: 10.1097/00007890-199310000-00004.
The development of progressive graft arteriosclerosis causes the majority of late deaths occurring in cardiac transplant recipients. The pathogenesis of this process remains unclear. In order to characterize the cellular composition of lesions progressively, we employed a model of graft arteriosclerosis in the rat involving untreated heterotopic cardiac allografts transplanted across minor histocompatibility barriers. Immunocytochemical studies were performed on arterial lesions in allografts removed at 15, 45, 75, and 120 days posttransplantation, using monoclonal antibodies specific for smooth muscle cells (HHF35, CGA7), monocytes/macrophages (ED1), T cells (W313), and endothelial cells (anti-vWf). We found areas of coronary intimal thickening demonstrated marked cellular heterogeneity. The earliest lesions involved the adherence of monocytes and T cells to the coronary endothelial surface. At later time points, we noted marked subendothelial accumulations of macrophages and occasional T cells in areas of intimal thickening. In contrast, smooth muscle cells were the major cell type identified in intimal lesions in 120-day-old allografts. Intimal macrophages are frequently seen in spontaneous human arteriosclerotic lesions; our findings suggest that macrophages, perhaps interacting with T cells, play an important role in the pathogenesis of graft arteriosclerosis.
进行性移植血管硬化的发展导致了心脏移植受者中大多数的晚期死亡。这一过程的发病机制仍不清楚。为了逐步明确病变的细胞组成，我们采用了大鼠移植血管硬化模型，该模型涉及跨越次要组织相容性屏障移植的未经处理的异位心脏同种异体移植物。使用针对平滑肌细胞（HHF35、CGA7）、单核细胞/巨噬细胞（ED1）、T细胞（W313）和内皮细胞（抗vWf）的单克隆抗体，对移植后15、45、75和120天取出的同种异体移植物中的动脉病变进行免疫细胞化学研究。我们发现冠状动脉内膜增厚区域表现出明显的细胞异质性。最早的病变涉及单核细胞和T细胞粘附于冠状动脉内皮表面。在后期时间点，我们注意到内膜增厚区域巨噬细胞和偶尔的T细胞在内皮下有明显积聚。相比之下，平滑肌细胞是120日龄同种异体移植物内膜病变中鉴定出的主要细胞类型。内膜巨噬细胞在人类自发性动脉粥样硬化病变中经常可见；我们的研究结果表明，巨噬细胞可能与T细胞相互作用，在移植血管硬化的发病机制中起重要作用。
