Feng L, Cheng F, Ye Z, Li S, He Y, Yao X, Tang Q, Li Y
Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, People's Republic of China.
Transplant Proc. 2006 Sep;38(7):2195-8. doi: 10.1016/j.transproceed.2006.06.013.
NKG2D, an activating receptor, may trigger NK and CD8+ T cells. Ligands for NKG2D and major histocompability complex class I chain-related antigen (MIC) have been reported to be expressed in rejected human renal allografts. MIC-NKG2D engagement may induce natural killer (NK) cell activation providing T-cell costimulation. We hypothesized that this interaction between innate and adaptive immunity may occur during kidney ischemia-reperfusion injury (IRI).
Male C57BL/6 mice after right renal resection were subjected to 35 minutes of left renal ischemia: the ischemic group. Sham-operated mice underwent the same protocol without vascular occlusion. The sham and ischemic kidneys were removed at 2 to 7, 10, 14, or 28 days postoperatively. The normal, sham, and ischemic kidney tissues were collected for reverse-transcriptase polymerase chain reaction, and immunohistochemistry analysis of MIC homologues in mice (Rae-1 and H60).
Compared with no expression in sham control and normal kidneys, IRI caused mRNA expression of Rae-1 from 2 to 10 days postoperatively and protein expression of Rae-1 from 2 to 14 days postoperatively in ischemic kidneys. We observed no expression of H60 mRNA or protein in any kidney.
H60 transcripts have been reported to be present in the BALB/c background but not in C57BL/6. We found IRI did not cause H60 mRNA on protein expression in C57BL/6 kidneys. Rae-1 was absent in normal C57BL/6 kidneys. The IRI-induced expression of the NKG2D ligand, Rae-1, might activate NK and CD8+ T cells. Our results suggested that MIC may be an important link between innate and adaptive immunity in kidney IRI.
激活受体NKG2D可触发自然杀伤细胞（NK）和CD8 + T细胞。据报道，NKG2D的配体和主要组织相容性复合体I类链相关抗原（MIC）在被排斥的人类肾移植中表达。MIC与NKG2D的结合可能诱导自然杀伤（NK）细胞活化，从而提供T细胞共刺激。我们推测，这种先天免疫与适应性免疫之间的相互作用可能发生在肾脏缺血再灌注损伤（IRI）期间。
右肾切除后的雄性C57BL/6小鼠接受35分钟的左肾缺血：即缺血组。假手术小鼠接受相同方案但不进行血管闭塞。在术后2至7天、10天、14天或28天切除假手术组和缺血组的肾脏。收集正常、假手术和缺血肾脏组织用于逆转录聚合酶链反应，以及对小鼠中MIC同源物（Rae-1和H60）进行免疫组织化学分析。
与假手术对照组和正常肾脏中无表达相比，IRI导致缺血肾脏在术后2至10天Rae-1的mRNA表达以及术后2至14天Rae-1的蛋白表达。我们在任何肾脏中均未观察到H60 mRNA或蛋白的表达。
据报道，H60转录本存在于BALB/c背景中，但不存在于C57BL/6中。我们发现IRI不会导致C57BL/6肾脏中H60 mRNA或蛋白表达。正常C57BL/6肾脏中不存在Rae-1。IRI诱导的NKG2D配体Rae-1的表达可能激活NK和CD8 + T细胞。我们的结果表明，MIC可能是肾脏IRI中先天免疫与适应性免疫之间的重要联系。
