Ishii E, Shimizu A, Kuwahara N, Arai T, Kataoka M, Wakamatsu K, Ishikawa A, Nagasaka S, Fukuda Y
Department of Analytic Human Pathlogy, Nippon Medical School, Tokyo, Japan.
Transplant Proc. 2010 Dec;42(10):4282-5. doi: 10.1016/j.transproceed.2010.09.081.
Lymphangiogenesis may be important for the cellular immune response in liver transplantation. In the present study, we examined lymphangiogenesis in liver allografts displaying acute cellular rejection (ACR), or long-term acceptance, or severe ACR plus antibody-mediated rejection (AMR). ACR and subsequent long-term graft acceptance developed in liver transplantations from DA to PVG rats without immunosuppression (mean survival time more than 90 days). Severe ACR and AMR developed in liver transplantations from DA to Lewis rats without immunosuppression (mean survival = 11 days). Normal DA donor livers before transplantation showed a small number of lymphatic vessels around portal veins. DA liver grafts in PVG showed ACR with lymphangiogenesis in portal areas and portal-portal bridging areas with cellular infiltration. Newly formed lymphatic vessels in ACR were characterized by proliferating endothelial cells with expression of the homeobox transcription factor PROX-1 and surrounded by discontinuous basement membranes. Thereafter, the infiltrates spontaneously disappeared, and the grafts survived more than 90 days. During the resolution of the cellular infiltration, expanded lymphatic vessels were packed with many lymphocytes. Thereafter, the number of lymphatic vessels decreased. In contrast, severe ACR and AMR in DA-to-Lewis transplantations showed lymphatic vessels disappeared with edema in the portal areas at day 11. In conclusion, lymphangiogenesis occurred during ACR. It may be involved in the resolution of ACR and reduction of inflammation. In severe ACR and AMR, lymphatic vessels were destroyed, which may be involved in persistent severe inflammation.
淋巴管生成可能对肝移植中的细胞免疫反应具有重要意义。在本研究中，我们检测了显示急性细胞排斥反应（ACR）、长期存活或严重ACR加抗体介导排斥反应（AMR）的肝移植同种异体移植物中的淋巴管生成情况。在未进行免疫抑制的情况下，从DA大鼠到PVG大鼠的肝移植中出现了ACR及随后的长期移植物存活（平均存活时间超过90天）。在未进行免疫抑制的情况下，从DA大鼠到Lewis大鼠的肝移植中出现了严重ACR和AMR（平均存活时间 = 11天）。移植前正常的DA供肝在门静脉周围显示少量淋巴管。PVG中的DA肝移植物表现为ACR，在门静脉区域和门静脉-门静脉桥接区域有淋巴管生成并伴有细胞浸润。ACR中新形成的淋巴管以内皮细胞增殖为特征，表达同源盒转录因子PROX-1，且被不连续的基底膜包围。此后，浸润细胞自发消失，移植物存活超过90天。在细胞浸润消退过程中，扩张的淋巴管内充满了许多淋巴细胞。此后，淋巴管数量减少。相比之下，DA到Lewis移植中的严重ACR和AMR在第11天时显示门静脉区域水肿，淋巴管消失。总之，ACR期间发生了淋巴管生成。它可能参与了ACR的消退和炎症减轻。在严重ACR和AMR中，淋巴管被破坏，这可能与持续的严重炎症有关。
