Ensminger Stephan M, Spriewald Bernd M, Steger Ulrich, Morris Peter J, Mak Tak W, Wood Kathryn J
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Transplantation. 2002 Nov 15;74(9):1267-73. doi: 10.1097/00007890-200211150-00012.
Platelet-endothelial cell adhesion molecule(PECAM)-1 (CD31) is expressed on the surface of endothelial cells, platelets, monocytes, neutrophils, and certain T-cell subsets. Treatment of endothelial cells with anti-PECAM-1 antibody inhibits leukocyte transmigration. This study was designed to test the hypothesis that, in transplantation, the absence of PECAM-1 expression on donor endothelial cells would reduce the number of leukocytes transmigrating into the allograft, thereby attenuating the development of transplant arteriosclerosis.
PECAM-1 and PECAM (C57BL/6/H2 ) abdominal aortic allografts were transplanted into BALB/c (H2 ) recipients; syngeneic grafts were used as controls. Aortic grafts were analyzed by performing morphometry, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction for the detection of intragraft cytokine mRNA production.
Intimal proliferation was exacerbated in PECAM-1 grafts (57+/-5% for PECAM-1 vs. 36+/-6% for PECAM-1; <0.005; n=6). The absence of PECAM-1 expression on donor endothelial cells did not reduce the overall number of graft-infiltrating cells significantly but instead resulted in a significant increase in infiltration by macrophages (F4/80 cells), leading to significantly elevated intragraft mRNA expression of inducible nitric oxide synthase. During the development of transplant arteriosclerosis, PECAM-1 donor endothelial cells were replaced by recipient PECAM-1 endothelial cells, a process that occurred only in the allogeneic situation. Endothelial replacement commenced 14 days after transplantation and was complete by day 30.
These data suggest that PECAM-1 expression by donor endothelial cells attenuates the development of transplant arteriosclerosis, possibly by affecting macrophage infiltration.
血小板内皮细胞黏附分子（PECAM）-1（CD31）在内皮细胞、血小板、单核细胞、中性粒细胞及某些T细胞亚群表面表达。用抗PECAM-1抗体处理内皮细胞可抑制白细胞迁移。本研究旨在验证以下假说：在移植过程中，供体内皮细胞上缺乏PECAM-1表达会减少迁移至同种异体移植物中的白细胞数量，从而减轻移植性动脉硬化的发展。
将PECAM-1和PECAM（C57BL/6/H2）腹主动脉同种异体移植物移植到BALB/c（H2）受体中；同基因移植物用作对照。通过形态计量学、免疫组织化学和定量逆转录聚合酶链反应分析主动脉移植物，以检测移植物内细胞因子mRNA的产生。
PECAM-1移植物中的内膜增生加剧（PECAM-1为57±5%，而PECAM-1为36±6%；<0.005；n = 6）。供体内皮细胞上缺乏PECAM-1表达并未显著减少移植物浸润细胞的总数，反而导致巨噬细胞（F4/80细胞）浸润显著增加，导致诱导型一氧化氮合酶的移植物内mRNA表达显著升高。在移植性动脉硬化发展过程中，PECAM-1供体内皮细胞被受体PECAM-1内皮细胞取代，这一过程仅发生在同种异体情况下。内皮细胞替代在移植后14天开始，至第30天完成。
这些数据表明，供体内皮细胞表达PECAM-1可能通过影响巨噬细胞浸润来减轻移植性动脉硬化的发展。
