不明原因自然流产与蜕膜NK细胞表面活化性受体表达的相关性研究

Correlation between the spontaneous abortion of unknown origin and the expression of surface natural cytotoxicity receptor on decidual NK cells

探讨不明原因自然流产患者蜕膜NK细胞杀伤活性与其细胞表面活化性受体NKp46、NKp44、NKp30和NKG2D表达的相关性。选取21例早孕不明原因自然流产患者为病例组,25例正常早孕人流妇女为对照组,收集两组的蜕膜组织,Ficoll密度梯度离心分离淋巴细胞,MACS磁珠分选CD3-CD56+NK细胞。以K562细胞为靶细胞,用细胞染色及流式细胞技术检测两组蜕膜NK细胞杀伤活性,用流式细胞技术检测两组蜕膜CD56brightCD16-NK和CD56dimCD16+NK细胞上活化性受体NKp46、NKp44、NKp30和NKG2D的表达,并与NK细胞杀伤活性进行相关性分析。结果:(1)早孕蜕膜NK细胞具有杀伤活性;(2)病例组蜕膜NK细胞的杀伤活性较正常对照组显著增强(P=0.014);(3)病例组蜕膜CD56brightCD16-NK细胞中NKp44的表达比正常对照组显著升高(P=0.021);病例组蜕膜CD56dimCD16+NK细胞中NKp46和NKp44的表达比正常对照组显著升高(分别P=0.026,P=0.041);其余活化性受体的表达两组未见明显差异;(4)蜕膜NK细胞杀伤功能与蜕膜CD56brightCD16-NK细胞中NKp44的表达呈显著正相关(r=0.677,P<0.05),和蜕膜CD56dimCD16+NK细胞中NKp46的表达呈显著正相关(r=0.634,P<0.05)。蜕膜NK细胞活化性受体NKp46和NKp44表达增加,从而使蜕膜NK细胞的杀伤功能增强可能在不明原因自然流产的发病中起重要作用。

To investigate the correlation btween the spontaneous abortion of unknown origin and the expression of surface natural cytotoxicity receptors on decidual NK cells. The decidual CD3^-CD56^＋NK cells from 21 cases of spontaneous abortion of unknown origin and from 25 normal pregnant women were isolated by Ficoll gradient centrifugatlon and magnetic cell sorting （MACS）, and the cytotoxicity of the decidual NK cells was assayed by cell staining and flow cytometry technique, using K562 cells as the target cells. The expressions of the natural cytotoxlclty receptors, such as NKp46, NKp44, NKp30, NKG2Don decidual CD56^brightCD16 NK cells and CD56^dimCD16^＋ NK cells were detected hy flow cytometry analysis. Correlation between the cytotoxlclty induced by NK cells and the expressions of the natural cytotoxicity receptors on ducldual NK cells were then analyzed. It was demonstrated that the decidual NK cells taken from preganant women showed cytotoxic activities, in which those in patients was significantly higher than that of the normal controls, and the expressions of NKp44 in ducldual CD56^bright CD16 NK cells was significantly higher in patients than those in normal controls; whereas, the expressions of NKp46 and NKp44 in decidual CD56^dim CD16^＋ NK cells were also higher in patients. However, there was no difference in the expressions of NKp30 and NKG2D receptors between these two groups. Both the expressions of NKp44 and NKp46 on decidual CD56^brightCD16 NK cells were positively correlated to the cytotoxic activities of decldual NK cells （r=0. 677, P〈0.0.5）. It is evident that the enhanced cytotoxlc activity of decidual NK cells may play an important role in the pathogenesis of the spontaneous a bortion of unknown origin.