Expression of tumor necrosis factor receptors in normal kidney and rejecting renal transplants
Expression of tumor necrosis factor receptors in normal kidney and rejecting renal transplants
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DOI：
10.1038/labinvest.3780364
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发表时间：
2001-11-01
影响因子：
5
通讯作者：
Bradley, JR
中科院分区：
文献类型：
--
作者：
Al-Lamki, RS;Wang, J;Bradley, JR
TNF信号转导级联的激活由TNF与两种细胞表面受体TNFR-1和TNFR-2中的任一种的相互作用引发。这两种受体的表达水平和调控已在培养细胞中进行了广泛的分析，但对TNFR的原位表达知之甚少。我们分析了TNFR-1和TNFR-2在正常人肾和发生急性细胞排斥反应的肾移植中的表达。免疫组化和免疫金电镜显示TNFR-1在正常肾脏肾小球内皮细胞上有强表达。TNFR-1和trans-Golgi网络的标记物（TGN-46）的免疫金共定位证明了TNFR-1在正常肾脏内皮细胞的高尔基复合体内，证实了我们先前对培养细胞的研究。TNFR-1在急性排斥肾的肾小球中表达缺失，但在急性排斥的同种异体移植物的肾小球中浸润的白细胞中检测到大量TNFR-1。相反，TNFR-2主要在急性排斥反应肾的远曲小管（DCT）上皮细胞中表达，靠近表达TNF的白细胞。TNF在正常肾组织中无表达，但在排斥反应肾组织中有表达。在浸润的白细胞和邻近的肾小管上皮细胞中发现TNF。原位杂交显示TNFR-1 mRNA在正常肾脏的肾小球和少数小动脉的内皮细胞内，而TNFR-2 mRNA在急性移植排斥反应的DCT的肾小管上皮细胞中被观察到。这些数据表明，在人肾脏中存在两种TNF受体的差异表达和调节。
Activation of the TNF signal transduction cascade is initiated by the interaction of TNF with either of two cell surface receptors, TNFR-1 and TNFR-2. The levels and regulation of expression of these two receptors has been extensively analyzed in cultured cells, but little is known of TNFR expression in situ. We analyzed the expression of TNFR-1 and -2 in normal human renal kidney and in renal transplants undergoing acute cellular rejection. Immunohistochemistry and immunogold electron microscopy indicated a strong expression of TNFR-1 on the endothelium of glomeruli of normal kidney. Immunogold colocalization for TNFR-1 and a marker of the trans-Golgi network (TGN-46) demonstrated TNFR-1 within the Golgi complex in endothelial cells in normal kidney, confirming our previous studies with cultured cells. TNFR-1 expression was lost in glomeruli from acutely rejecting kidney, but TNFR-1 was detected in abundance on infiltrating leukocytes in the interstitium of allografts with acute rejection. In contrast, TNFR-2 was demonstrated predominantly in epithelia[ cells of distal convoluted tubule (DCT) in acute rejection kidney near TNF-expressing leukocytes. TNF was absent in normal kidney, but present in rejecting allograft. TNF was found in infiltrating leukocytes and in adjacent tubular epithelia[ cells. In situ hybridization showed TNFR-1 mRNA within the endothelium of the glomeruli and of a few arterioles in normal kidney, whereas TNFR-2 mRNA was seen in tubular epithelial cells of the DCT in acute transplant rejection. These data reveal that there is both differential expression and regulation of the two TNF receptors in human kidney.