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排斥和自发接受的大鼠肝脏同种异体移植中肝窦内皮细胞的功能

Liver sinusoidal endothelial cell function in rejected and spontaneously accepted rat liver allografts.

作者信息

Ge Xupeng, Nowak Grzegorz, Ericzon Bo-Göran, Sumitran-Holgersson Suchitra

机构信息

Division of Transplantation Surgery, Karolinska University Hospital-Huddinge, Karolinska Institute, Stockholm, Sweden.

出版信息

Transpl Int. 2008 Jan;21(1):49-56. doi: 10.1111/j.1432-2277.2007.00569.x. Epub 2007 Oct 10.

Abstract

Studies have suggested that liver sinusoidal endothelial cells (LSEC) may play an important role in tolerance induction. In this study, we evaluated the functional difference of LSEC in rejection and spontaneous acceptance of liver allografts by using rat liver transplant model. LSEC function was determined by circulating hyaluronic acid (HA) levels and fluorescein isothiocyanate-labeled formaldehyde-treated serum albumin (FITC-FSA) uptake. Additional parameters include the number of circulating lymphocytes and LSEC apoptosis. In spontaneously accepted group, we found (i) significantly lower serum HA levels (P = 0.002), (ii) a more rapid uptake of FITC-FSA, and (iii) a reduced number of circulating CD8a+ cells when compared with the rejection group. Strikingly, HA levels in spontaneously accepted group are even lower than syngeneic control group. Further investigation revealed that interleukin-1beta, a cytokine that promotes LSEC function, was higher in DA than in Lewis rats. In summary, our study demonstrates that LSEC function is better preserved in spontaneously accepted rat liver allografts than in those which are rejected. These findings warrant further studies to verify if LSEC actively contributes to liver transplant outcome or just a target of different immunologic responses.

摘要

研究表明,肝窦内皮细胞(LSEC)可能在诱导免疫耐受中发挥重要作用。在本研究中,我们通过大鼠肝移植模型评估了LSEC在肝同种异体移植排斥反应和自发接受过程中的功能差异。LSEC功能通过循环透明质酸(HA)水平和异硫氰酸荧光素标记的经甲醛处理的血清白蛋白(FITC-FSA)摄取来确定。其他参数包括循环淋巴细胞数量和LSEC凋亡。在自发接受组中,我们发现:(i)血清HA水平显著降低(P = 0.002);(ii)FITC-FSA摄取更快;(iii)与排斥组相比,循环CD8a+细胞数量减少。引人注目的是,自发接受组的HA水平甚至低于同基因对照组。进一步研究发现,促进LSEC功能的细胞因子白细胞介素-1β在DA大鼠中高于Lewis大鼠。总之,我们的研究表明,自发接受的大鼠肝同种异体移植中LSEC功能比被排斥的移植中保存得更好。这些发现值得进一步研究,以验证LSEC是积极影响肝移植结果还是仅仅是不同免疫反应的靶点。

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