Ye Z, Feng L, Huang S, Li S, He Y, Li Y
Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China.
Transplant Proc. 2006 Sep;38(7):2168-71. doi: 10.1016/j.transproceed.2006.06.096.
It has been reported that the MHC class I chain-related antigen (MIC), a ligand of NKG2D, an activating receptor of natural killer cells, is expressed on rejected renal allografts. This study investigated whether heart transplantation induced expression of a homologue of MIC (H60) in outbred Kun Ming (KM) mice, widely used in China, and whether CsA had an influence on the process.
Forty-eight KM female mice were divided into untreated and CsA-treated groups, after cervical heart allotransplantation. Grafts were harvested 1, 3, 5, and 7 days postoperatively. H60 mRNA was analyzed by RT-PCR, and the protein detected by immunohistochemistry.
Compared with no mRNA expression in the normal heart, H60 mRNA was observed at day 5 and upregulated on day 7 in the untreated group. It was detected on day 3, peaked on day 5, but was lower than untreated group, and decreased on day 7 in the CsA-treated group. H60 protein was detected in cardiocytes only on day 7 in the untreated group.
Our study suggested that expression of the NKG2D ligand, H60, may activate natural killer cells playing a significant role in innate immunity associated with transplantation. The early expression of H60 mRNA on day 3 in the CsA-treated group might relate to the toxicity of CsA. The expression peaked on day 5 and decreased on day 7, possibly induced by CsA. The results suggested that H60 might be a new target for prevention of rejection.
据报道，自然杀伤细胞激活受体NKG2D的配体——MHC I类链相关抗原（MIC）在移植肾排斥反应中表达。本研究调查了在中国广泛使用的远交系昆明（KM）小鼠心脏移植后是否会诱导MIC同源物（H60）的表达，以及环孢素A（CsA）是否会对该过程产生影响。
48只雌性KM小鼠在进行颈部心脏异体移植移植后，分为未处理组和CsA处理组。术后1、3、5和7天采集移植物。通过逆转录聚合酶链反应（RT-PCR）分析H60 mRNA，并通过免疫组织化学检测蛋白质。
与正常心脏中无mRNA表达相比，未处理组在术后第5天观察到H60 mRNA，第7天上调。CsA处理组在术后第3天检测到H60 mRNA，第5天达到峰值，但低于未处理组，第7天下降。未处理组仅在第7天在心肌细胞中检测到H60蛋白。
我们的研究表明，NKG2D配体H60的表达可能激活自然杀伤细胞，在与移植相关的固有免疫中发挥重要作用。CsA处理组在术后第3天H60 mRNA的早期表达可能与CsA的毒性有关。其表达在第5天达到峰值，第7天下降，可能是由CsA诱导的。结果表明，H60可能是预防排斥反应的新靶点。
