DNA FROM BACTERIA, BUT NOT FROM VERTEBRATES, INDUCES INTERFERONS, ACTIVATES NATURAL-KILLER-CELLS AND INHIBITS TUMOR-GROWTH
DNA FROM BACTERIA, BUT NOT FROM VERTEBRATES, INDUCES INTERFERONS, ACTIVATES NATURAL-KILLER-CELLS AND INHIBITS TUMOR-GROWTH
复制标题
DOI：
10.1111/j.1348-0421.1992.tb02102.x
复制
发表时间：
1992-01-01
影响因子：
2.6
通讯作者：
TOKUNAGA, T
中科院分区：
文献类型：
--
作者：
YAMAMOTO, S;YAMAMOTO, T;TOKUNAGA, T
通过与前述相同的程序，从 6 种细菌和 2 种脊椎动物（小牛和鲑鱼）的细胞中提取和纯化核酸部分。当 BALB/c 小鼠的脾细胞与任一细菌的核酸片段一起孵育时，细胞的自然杀伤 (NK) 活性显着升高，并且细胞产生激活巨噬细胞和抑制病毒生长的因子。结果表明，激活巨噬细胞的因子是干扰素（IFN）-γ，抑制病毒生长的因子是IFN-α/β。另一方面，来自任一脊椎动物细胞的核酸部分没有表现出这样的活性。用 DNase（而非 RNase）预处理细菌核酸部分，完全消除了生物活性。细菌核酸的活性不受脂多糖(LPS)抑制剂多粘菌素B的存在的影响，并且不仅BALB/c小鼠的脾细胞被激活，而且LPS不敏感的C3H/HeJ小鼠的脾细胞也被激活，这表明该级分的活性不是归因于可能污染到级分中的LPS，而是归因于DNA本身。病灶内注射细菌 DNA 组分导致小鼠 IMC 肿瘤消退，但注射脊椎动物 DNA 组分却没有。这些发现促使我们检查来自其他实验室提供或从制造商处购买的各种动植物 DNA 样本的生物活性。来自5种细菌、2种病毒和4种无脊椎动物细胞的所有DNA样本都在小鼠脾脏调用中增强了NK活性并或多或少地诱导了IFN，而来自10种脊椎动物（包括3种鱼类和5种哺乳动物）的DNA则没有表现出这种活性。 两种植物的 DNA 也处于非活性状态。基于我们之前的发现，讨论了解释不同细胞来源的 DNA 的不同生物活性的可能机制，即使用合成的 30 聚体寡核苷酸诱导 IFN 和激活 NK 细胞需要具有 G-C 基序的特定回文序列。
The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified by the same procedures as described previously. When the spleen cells from BALB/c mice were incubated with the nucleic acid fraction from either of the bacteria, natural killer (NK) activity of the cells was remarkably elevated and the cells produced factors to activate macrophages and to inhibit viral growth. It was shown that the factor to activate macrophages was interferon (IFN)-gamma and that to inhibit viral growth was IFN-alpha/beta. On the other hand, the nucleic acid fraction from either of the vertebrate cells did not show such activities. Pretreatment of the bacterial nucleic acid fraction with DNase, but not with RNase, abrogated completely the biological activities. The activities of the bacterial nucleic acid were not influenced by the presence of polymyxin B, an inhibitor of lipopolysaccharide (LPS), and the spleen cells from not only BALB/c mice but also LPS-insensitive C3H/HeJ mice were activated, indicating that the activities of the fraction were not ascribed to LPS contaminated possibly into the fraction, but to DNA itself. Intralesional injection with the bacterial DNA fraction caused regression of mouse IMC tumors, but the injection with the vertebrate DNA fraction did not. These findings prompted us to examine the biological activities of DNA samples from a variety of animals and plants, which were provided from other laboratories or purchased from manufacturers. All of the DNA samples from cells of 5 kinds of bacterium, 2 of virus and 4 of invertebrate augmented NK activity and induced IFN, more or less, in mouse spleen calls, while the DNA from 10 kinds of vertebrate, including 3 of fish and 5 of mammal, showed no such activities. The DNA from 2 species of plants, were also inactive. Possible mechanisms to explain the different biological activities of DNA from different cell sources were discussed based on our previous finding that the particular palindromic sequences with a G-C motif (s) are required for induction of IFNs and activation of NK cells with synthetic 30-mer oligonucleotides.