Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan.
Microbes Infect. 2014 Mar;16(3):196-202. doi: 10.1016/j.micinf.2013.11.012. Epub 2013 Dec 3.
Extracellular nucleotides such as adenosine 5'-triphospate (ATP) and uridine 5'-triphosphate (UTP) interact with P2 purinergic receptors on the surface of phagocytic cells and induce various physiological reactions. In this study, the production of antibody in mice immunized with an inactivated rabies vaccine containing these nucleotides was investigated. Injection of inactivated rabies vaccine with UTP, but not with ATP, induced significantly higher serum antibody production in mice. The enhancement of antibody production by UTP was inhibited by an anti-P2Y4 receptor antibody. In an air pouch experiment, UTP treatment increased the number of monocytes and macrophages infiltrating the pouch and up-regulated the gene expression of IL-4 and IL-13 in the regional lymph nodes. These results suggested that UTP admixed with rabies vaccine activates Th2 cells and induces a humoral immune response. Furthermore, the survival rate of mice immunized with a rabies vaccine admixed with UTP before rabies virus challenge was slightly higher than that of control mice. In conclusion, UTP can act as a vaccine adjuvant to enhance antibody production against the rabies virus in mice.
细胞外核苷酸,如腺苷 5'-三磷酸 (ATP) 和尿苷 5'-三磷酸 (UTP),与吞噬细胞表面的 P2 嘌呤能受体相互作用,诱导各种生理反应。在这项研究中,研究了用含有这些核苷酸的灭活狂犬病疫苗免疫的小鼠产生抗体的情况。与 ATP 不同,UTP 的加入可显著提高小鼠的血清抗体产生。UTP 诱导的抗体产生增强可被抗 P2Y4 受体抗体抑制。在气囊实验中,UTP 处理增加了单核细胞和巨噬细胞浸润气囊的数量,并上调了区域淋巴结中 IL-4 和 IL-13 的基因表达。这些结果表明,与狂犬病疫苗混合的 UTP 激活了 Th2 细胞,并诱导了针对狂犬病病毒的体液免疫反应。此外,在狂犬病病毒攻击前用 UTP 混合狂犬病疫苗免疫的小鼠的存活率略高于对照小鼠。总之,UTP 可以作为疫苗佐剂,增强小鼠对狂犬病病毒的抗体产生。