Okamura H, Nagata K, Komatsu T, Tanimoto T, Nukata Y, Tanabe F, Akita K, Torigoe K, Okura T, Fukuda S
Department of Bacteriology, Hyogo College of Medicine, Nishinomiya, Japan.
Infect Immun. 1995 Oct;63(10):3966-72. doi: 10.1128/iai.63.10.3966-3972.1995.
Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.
给用痤疮丙酸杆菌处理过的小鼠注射单克隆抗 CD3 抗体，可诱导其循环系统分泌高水平的γ干扰素（IFN-γ），而在未处理的小鼠中则不会诱导出明显的释放。为了分析这些经细菌处理的小鼠中 IFN-γ 的这种高水平诱导现象，我们研究了可能涉及的因素。在用痤疮丙酸杆菌处理并随后用脂多糖攻击的小鼠肝脏提取物中，观察到一种在 T 细胞中诱导 IFN-γ 的活性。在此，我们从肝脏提取物中纯化出一种 IFN-γ 诱导因子，使其达到同质状态并对其进行了表征。其分子量为 18 至 19 kDa，pI 为 4.9。测定了其 NH2 末端部分的氨基酸序列，结果显示与 EMBL、GenBank 和 PIR 数据库中的任何蛋白质均无相似性。在先前报道具有 IFN-γ 诱导活性且表观分子量为 75 kDa 的血清因子中也证实了存在相同的分子。此外，在还原条件下，这种血清因子的活性在含有 18 至 19 kDa 蛋白质的级分中得以恢复，并且显示其 NH2 末端氨基酸序列与肝脏提取物中的因子相同。除了诱导 IFN-γ 的能力外，这种蛋白质还增强了脾细胞中的 T 细胞增殖和 NK 活性。因此，它的几种生物学活性显然与白细胞介素-12 的活性相似。这些结果表明，这种在体外对 IFN-γ 产生具有明显共刺激活性的新型蛋白质，在体内因痤疮丙酸杆菌处理而升高。这种因子可能是由脂多糖刺激从产生细胞中释放出来的，可能参与了痤疮丙酸杆菌处理的小鼠中 IFN-γ 的高水平诱导。
