Black P L, Henderson E E, Pfleiderer W, Charubala R, Suhadolnik R J
J Immunol. 1984 Nov;133(5):2773-7.
Interferon (IFN) augments the lytic activity of natural killer (NK) cells, inhibits the transformation of human peripheral blood lymphocytes (PBL) by Epstein Barr virus (EBV), and induces a 2',5'-oligoadenylate (2',5'-An) synthetase. Exogenous 2',5'-An by itself can inhibit the transformation of human PBL by EBV. The present studies report that 2',5'-An and its cordycepin analog also augmented the tumoricidal activity of human NK cells. Incubation of nylon wool-passed PBL for 1 to 2 hr with the 5'-dephosphorylated core trimer of 2',5'-An boosted natural killing of tumor target cells modestly, but consistently. The cordycepin analog (3'-deoxyadenylate) also augmented NK activity. The optimal concentration both of 2',5'-A3 core and of 2',5'-3'dA3 core was 50 microM, and the optimal time for this effect was 2 hr of treatment. Kinetic analysis revealed that 2',5'-A3 core increased the lytic rate of NK cells by about one-third. This increase was due to an even greater increase (about 50%) in the lytic activity of individual NK cells, coupled with a slight decrease in the number of actual NK effector cells. In contrast, 3',5'-A3 core did not increase NK activity even at 300 microM, at which point it was toxic. In addition, to rule out a pro-drug effect as the basis for the boosting of NK activity by 2',5'-A3 core and by 2',5'-3'dA3 core, the effect of adenosine and cordycepin monomers on NK activity was tested. Neither adenosine nor cordycepin, tested at 150 microM (three times the optimal concentration of the trimer cores), boosted NK activity. The addition of 2'-deoxycoformycin (2 microM) had no effect on the actions of adenosine and cordycepin monomers. The data presented here demonstrate that 2',5'-A3 core and its analog 2',5'-3'dA3 core have another IFN-like action, augmentation of NK activity, in addition to inhibiting EBV-induced transformation.
干扰素（IFN）可增强自然杀伤（NK）细胞的裂解活性，抑制爱泼斯坦-巴尔病毒（EBV）诱导的人外周血淋巴细胞（PBL）转化，并诱导2',5'-寡腺苷酸（2',5'-An）合成酶。外源性2',5'-An本身可抑制EBV诱导的人PBL转化。本研究报告称，2',5'-An及其虫草素类似物也增强了人NK细胞的杀肿瘤活性。用2',5'-An的5'-去磷酸化核心三聚体孵育尼龙毛柱过滤后的PBL 1至2小时，适度但持续地增强了对肿瘤靶细胞的自然杀伤作用。虫草素类似物（3'-脱氧腺苷酸）也增强了NK活性。2',5'-A3核心和2',5'-3'dA3核心的最佳浓度均为50微摩尔，产生这种作用的最佳时间为处理2小时。动力学分析表明，2',5'-A3核心使NK细胞的裂解速率提高了约三分之一。这种提高是由于单个NK细胞的裂解活性有更大幅度的提高（约50%），同时实际NK效应细胞数量略有减少。相比之下，即使在300微摩尔时，3',5'-A3核心也不会增加NK活性，此时它具有毒性。此外，为了排除前体药物效应是2',5'-A3核心和2',5'-3'dA3核心增强NK活性的基础，测试了腺苷和虫草素单体对NK活性的影响。在150微摩尔（三聚体核心最佳浓度的三倍）下测试的腺苷和虫草素均未增强NK活性。添加2'-脱氧助间型霉素（2微摩尔）对腺苷和虫草素单体的作用没有影响。此处呈现的数据表明，2',5'-A3核心及其类似物2',5'-3'dA3核心除了抑制EBV诱导的转化外，还具有另一种类似IFN的作用，即增强NK活性。
