Enhancement of antibody production against rabies virus by uridine 5′-triphosphate in mice

Enhancement of antibody production against rabies virus by uridine 5′-triphosphate in mice
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DOI:
10.1016/j.micinf.2013.11.012
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发表时间:
2014-03-01
影响因子:
5.8
通讯作者:
Sunden, Yuji
Sunden, Yuji
中科院分区:
医学3区
文献类型:
--
作者:
Iwaki, Yoshimi;Sakai, Yusuke;Sunden, Yuji

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细胞外核苷酸如5'-三磷酸腺苷(ATP)和5'-三磷酸尿苷(UTP)与吞噬细胞表面的P2嘌呤受体相互作用,诱发各种生理反应。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体内抗体的产生。注射含有 UTP(而非 ATP)的灭活狂犬病疫苗,可诱导小鼠产生显着更高的血清抗体。 UTP 产生的抗体的增强被抗 P2Y4 受体抗体抑制。在气囊实验中,UTP 处理增加了浸润气囊的单核细胞和巨噬细胞的数量,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,UTP 与狂犬病疫苗混合可激活 Th2 细胞并诱导体液免疫反应。此外,在狂犬病病毒攻击前用与UTP混合的狂犬病疫苗免疫的小鼠的存活率略高于对照小鼠。总之,UTP可以作为疫苗佐剂来增强小鼠体内针对狂犬病病毒的抗体产生。 (C) 2013 年巴斯德研究所。由 Elsevier Masson SAS 出版。版权所有。
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. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.