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聚肌苷酸的干扰素诱导活性

Interferon inducing activity of polyinosinic acid.

作者信息

De Clercq E, Stollar B D, Thang M N

出版信息

J Gen Virol. 1978 Jul;40(1):203-12. doi: 10.1099/0022-1317-40-1-203.

Abstract

Although poly(I) is generally considered to be inactive as an interferon inducer, we have found several authentic poly(I) preparations to be effective inducers. Their interferon inducing ability varied considerably from one cell system to another. In human diploid fibroblasts, primed with interferon and superinduced by cycloheximide and actinomycin D, all active poly(I) samples proved nearly as effective in inducing interferon as poly(I).poly(C). In primary rabbit kidney cell cultures, the active poly(I) samples were either as active, or 3 to 30 times less active than poly(I).poly(C). In intact rabbits they were 100 times less active than poly(I).poly(C). Except for one particular sample, all active poly(I) preparations were inferior to poly(I).poly(C) when assayed for interferon induction in interferon-treated mouse L cells; in DEAE-dextran-treated L cells, they induced little, if any, interferon. The poly(I) inducers of interferon were considerably more susceptible to degradation by TI ribonuclease, pancreatic ribonuclease and human serum nuclease(s) than was poly(I).poly(C) when assayed under the same conditions. Due to their limited half-life time in biological fluids, poly(I) analogues such as those described here may offer a greater safety margin in clinical use than poly(I).poly(C).

摘要

尽管聚肌苷酸(poly(I))通常被认为作为干扰素诱导剂是无活性的,但我们发现几种纯的聚肌苷酸制剂是有效的诱导剂。它们诱导干扰素的能力在不同细胞系统中差异很大。在用人干扰素预处理并用环己酰亚胺和放线菌素D超诱导的人二倍体成纤维细胞中,所有活性聚肌苷酸样品在诱导干扰素方面几乎与聚肌苷酸-聚胞苷酸(poly(I).poly(C))一样有效。在原代兔肾细胞培养物中,活性聚肌苷酸样品的活性与聚肌苷酸-聚胞苷酸相同,或者比其低3至30倍。在完整的兔子体内,它们的活性比聚肌苷酸-聚胞苷酸低100倍。除了一个特定样品外,在经干扰素处理的小鼠L细胞中检测干扰素诱导活性时,所有活性聚肌苷酸制剂都不如聚肌苷酸-聚胞苷酸;在经DEAE-葡聚糖处理的L细胞中,它们几乎不诱导干扰素(如果有诱导的话)。在相同条件下检测时,干扰素的聚肌苷酸诱导剂比聚肌苷酸-聚胞苷酸更容易被TI核糖核酸酶、胰核糖核酸酶和人血清核酸酶降解。由于它们在生物流体中的半衰期有限,本文所述的聚肌苷酸类似物在临床应用中可能比聚肌苷酸-聚胞苷酸具有更大的安全边际。

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