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目的研究干扰素(IFN)对真性红细胞增多症(PV)患者外周血单个核细胞(PBMNC)的自然杀伤(NK)细胞活性及肿瘤坏死冈子相关凋亡诱导配体(TRAIL)等凋亡诱导基因表达的调节作用。方法取12例 PV 患者 PBMNC,用乳酸脱氢酶释放法检测 NK 细胞活性并计算裂解单位(LU),用 RNA 酶保护分析法检测 TRAIL 及其他凋亡诱导基因的表达。结果 PV 患者 PBMNC 的 NK 细胞活性在未经处理组为(152.0±146.6)LU,IFNα1b 及 IFNα2b 处理组分别为(250.9±197.4)LU 和(355.9±249.9)LU,与未处理组相比均显著升高(P<0.05和 P<0.01)。而 PV 患者的 PBMNC 经过IFNα1b及 IFNα2b 刺激后,TRAIL mRNA 的表达明显增加,且 IFNα上调 FLICE,DR3,DR4和TNFRp55基因表达,诱导 FasL,Fas,TRADD 和 RIP 基因的表达。为了确定 TRAIL 在 IFNα诱导的 NK细胞活性中所起的作用,应用中和实验表明 TRAIL 受体 DR4-Fc 及 DR5-Fc 多肽能够部分阻断 IFNα2b提高的 NK 细胞活性。结论 IFNα诱导/上调 TRAIL 及其他凋亡诱导基因在 PV 患者 PBMNC 的表达,并介导 IFNα提高的 NK 细胞活性,这可能是 IFNα治疗 PV 的机制之一。
Objective To study the natural killer (NK) cell activity of peripheral blood mononuclear cells (PBMNC) induced by interferon (IFN) in peripheral blood mononuclear cells (PBMNC) in patients with polycythemia vera (PVMN) and the apoptosis induction of tumor necrosis factor related apoptosis inducing ligand (TRAIL) Modulation of gene expression. Methods The PBMNC of 12 patients with PV were obtained. The activity of NK cells was measured by lactate dehydrogenase release assay and the unit of LU was calculated. The expression of TRAIL and other apoptosis-inducing genes were detected by RNase protection assay. Results The NK cell activity of PBMNC in patients with PV was (152.0 ± 146.6) LU, IFNα1b and IFNα2b were (250.9 ± 197.4) LU and (355.9 ± 249.9) LU, respectively, which were significantly higher than those in untreated group Increased (P <0.05 and P <0.01). However, the expression of TRAIL mRNA was significantly increased in PBMNC of patients with PV induced by IFNα1b and IFNα2b, and IFNα up-regulated the expression of FLICE, DR3, DR4 and TNFRp55 and induced the expression of FasL, Fas, TRADD and RIP. To determine the role of TRAIL in IFNa-induced NK cell activity, neutralizing experiments were performed to demonstrate that TRAIL receptors DR4-Fc and DR5-Fc polypeptides partially blocked the IFN [alpha] 2b-enhanced NK cell activity. Conclusion IFNα induces / up-regulates the expression of TRAIL and other apoptosis-inducing genes in PBMNC of PV patients and mediates the increase of NK cell activity by IFNα, which may be one of the mechanisms of IFNα in the treatment of PV.