Nagakawa Yuichi, Nomoto Shuji, Kato Yukihiko, Montgomery Robert A, Williams George Melville, Klein Andrew S, Sun Zhaoli
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Transplant. 2004 Dec;4(12):1949-57. doi: 10.1111/j.1600-6143.2004.00621.x.
Early and accurate detection of acute cellular rejection (ACR) is important in the management of liver allograft recipients. We hypothesized that expression of allograft inflammatory factor (AIF)-1 would be associated with liver allograft rejection as previous studies have shown that a relationship exists between kidney and heart transplantation. Indeed using rat orthotopic transplant models we found that the expression of allograft inflammatory factor-1 (AIF-1) can be detected in both allograft and peripheral blood leukocytes with peak levels detected 7 days following liver transplantation. Interestingly, AIF-1 expression increased 2-fold in acutely rejecting liver allografts compared to chronically accepted livers on days 5, 7 and 10 after transplantation. AIF-1 expression in peripheral blood leukocytes was also significantly greater in the rejection model than in the acceptance model. Flow cytometric analysis of peripheral blood leukocytes demonstrated that AIF-1 was expressed in ED2-positive cells, a marker for Kupffer cells. In vitro studies showed that AIF-1 expression in Kupffer cells was up-regulated by coculture with Th1 cytokines. However, neither LPS nor Escherichia coli (E. coli) administration had an affect on AIF-1 expression. These data indicate that high levels of AIF-1 expression reflect aggressive liver allograft rejection and suggest a role for monitoring AIF-1 in peripheral blood leukocytes as a monitor for increased immunosuppression.
早期准确检测急性细胞排斥反应（ACR）对于肝移植受者的管理至关重要。我们推测同种异体移植炎症因子（AIF）-1的表达可能与肝移植排斥反应有关，因为先前的研究表明肾移植和心脏移植之间存在这种关系。事实上，通过大鼠原位移植模型，我们发现同种异体移植炎症因子-1（AIF-1）在同种异体移植组织和外周血白细胞中均可检测到，肝移植后7天达到峰值水平。有趣的是，在移植后第5、7和10天，与长期存活的肝移植相比，急性排斥的肝移植中AIF-1表达增加了2倍。排斥模型中外周血白细胞中的AIF-1表达也明显高于接受模型。外周血白细胞的流式细胞术分析表明，AIF-1在ED2阳性细胞中表达，ED2是库普弗细胞的标志物。体外研究表明，与Th1细胞因子共培养可上调库普弗细胞中AIF-1的表达。然而，给予LPS或大肠杆菌（E. coli）均对AIF-1表达无影响。这些数据表明，高水平的AIF-1表达反映了严重的肝移植排斥反应，并提示监测外周血白细胞中的AIF-1可作为免疫抑制增加的监测指标。
