Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.
Int J Oncol. 2012 Apr;40(4):1285-90. doi: 10.3892/ijo.2011.1315. Epub 2011 Dec 22.
Natural-killer group 2 (NKG2), a natural killer (NK) cell receptor, plays a critical role in regulating NK cytotoxicity. In this study, we investigated the expression levels of natural killer group 2 member A (NKG2A) and natural killer group 2 member D (NKG2D) in NK cells as well as the regulatory function of NKG2D in patients with colorectal cancer (CRC). Sixty-two CRC patients and 32 healthy controls were enrolled in this study. The expression levels of NKG2A and NKG2D mRNA in peripheral blood mononuclear cells (PBMCs) were investigated using real-time PCR. Flow cytometry was performed to assay the levels of NKG2A and NKG2D proteins in NK cells. The levels of NKG2D mRNA in PBMCs in the patients were significantly lower than those in the controls [mean ± SD, 1.11 ± 0.60 (CRC patients) vs. 1.65 ± 0.71 (healthy controls); p < 0.01], whereas the 2 groups showed no apparent difference in the levels of NKG2A mRNA (p>0.05). In addition, the patients showed significantly lower NKG2D levels in NK cells than the controls did (71.23% ± 8.31% [CRC patients] vs. 79.39% ± 5.58% [healthy controls]; p < 0.01). However, we observed no distinct difference in the NKG2A expression levels in NK cells between the 2 groups (p> 0.05). Notably, blockage of NKG2D signaling with anti-NKG2D antibodies ex vivo resulted in decreased cytotoxicity and CD107a degranulation. Our data revealed that the decrease in NKG2D expression levels may have been associated with suppression of NK cell activity in CRC patients.
自然杀伤细胞群 2（NKG2）是一种自然杀伤（NK）细胞受体，在调节 NK 细胞毒性方面发挥着关键作用。在这项研究中，我们研究了 NK 细胞中自然杀伤细胞群 2 成员 A（NKG2A）和自然杀伤细胞群 2 成员 D（NKG2D）的表达水平，以及 NKG2D 在结直肠癌（CRC）患者中的调节功能。纳入了 62 例 CRC 患者和 32 名健康对照者。采用实时 PCR 检测外周血单个核细胞（PBMCs）中 NKG2A 和 NKG2D mRNA 的表达水平。采用流式细胞术检测 NK 细胞中 NKG2A 和 NKG2D 蛋白的水平。患者 PBMCs 中 NKG2D mRNA 的水平明显低于对照组[均数 ± 标准差，1.11 ± 0.60（CRC 患者）比 1.65 ± 0.71（健康对照）；p < 0.01]，而两组间 NKG2A mRNA 水平无明显差异（p>0.05）。此外，患者 NK 细胞中 NKG2D 水平明显低于对照组[71.23% ± 8.31%（CRC 患者）比 79.39% ± 5.58%（健康对照）；p < 0.01]。然而，两组间 NK 细胞中 NKG2A 表达水平无明显差异（p>0.05）。值得注意的是，体外阻断 NKG2D 信号通路用抗 NKG2D 抗体导致细胞毒性和 CD107a 脱颗粒减少。我们的数据表明，NKG2D 表达水平的降低可能与 CRC 患者 NK 细胞活性的抑制有关。
