Pratt J R, Abe K, Miyazaki M, Zhou W, Sacks S H
Department of Nephrology and Transplantation, King's College, University of London, Guy's Hospital, London, United Kingdom.
Am J Pathol. 2000 Sep;157(3):825-31. doi: 10.1016/S0002-9440(10)64596-8.
Recent evidence has implicated complement in renal transplant injury and identified the kidney as a source of complement components. We therefore investigated the local gene expression of complement component C3, pivotal to complement activation pathways and a mediator of inflammatory injury, in a rat renal transplant model. By reverse transcriptase-polymerase chain reaction, the expression of C3 mRNA increased in two phases. The first phase coincided with post-ischemic injury over 2 days post-transplantation and was localized by in situ hybridization to vessels and glomerular mesangial cells in allogeneic and syngeneic (control) kidney transplants. In allografts only, a second phase was found in tubular epithelial cells, glomerular parietal cells, vessel walls and some infiltrating cells, which peaked on day 4 together with rapid influx of leukocytes, tubule cell damage, the induction of interleukin-2 and interferon-gamma mRNA, and the up-regulation of tumor necrosis factor-alpha and interleukin-1beta mRNA in the graft. In vitro studies showed that interleukin-2 and interferon-gamma up-regulate C3 production in renal tubule cells. We conclude that post-ischemic injury led to transient up-regulation of glomerular expression of C3 mRNA. Subsequent cellular rejection was associated with tubulointerstitial/glomerular parietal cell expression of C3 mRNA. This differential expression of local C3, immediately post-transplant or associated with acute rejection, may have implications for putative therapeutic complement inhibition in clinical transplantation.
最近的证据表明补体与肾移植损伤有关，并确定肾脏是补体成分的来源。因此，我们在大鼠肾移植模型中研究了补体成分C3的局部基因表达，C3是补体激活途径的关键成分和炎症损伤的介质。通过逆转录聚合酶链反应，C3 mRNA的表达分两个阶段增加。第一阶段与移植后2天内的缺血后损伤同时发生，通过原位杂交定位在同种异体和同基因（对照）肾移植的血管和肾小球系膜细胞中。仅在同种异体移植中，在肾小管上皮细胞、肾小球壁层细胞、血管壁和一些浸润细胞中发现了第二阶段，在第4天达到峰值，同时白细胞迅速流入、肾小管细胞损伤、白细胞介素-2和干扰素-γ mRNA的诱导以及移植中肿瘤坏死因子-α和白细胞介素-1β mRNA的上调。体外研究表明，白细胞介素-2和干扰素-γ上调肾小管细胞中C3的产生。我们得出结论，缺血后损伤导致肾小球C3 mRNA表达短暂上调。随后的细胞排斥反应与肾小管间质/肾小球壁层细胞C3 mRNA的表达有关。移植后立即出现或与急性排斥反应相关的局部C3的这种差异表达，可能对临床移植中假定的治疗性补体抑制有影响。
