Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
PLoS One. 2013 May 22;8(5):e63759. doi: 10.1371/journal.pone.0063759. Print 2013.
It has been established that Adenosine-5'-triphosphate (ATP) can activate the NLRP3 inflammasome. However, the physiological effect of extracellular ATP on NLRP3 inflammasome activation has not yet been investigated. In the present study, we found that ATP was indeed released during bacterial infection. By using a murine peritonitis model, we also found that ATP promotes the fight against bacterial infection in mice. ATP induced the secretion of IL-1β and chemokines by murine bone marrow-derived macrophages in vitro. Furthermore, the intraperitoneal injection of ATP elevated the levels of IL-1β and chemokines in the mouse peritoneal lavage. Neutrophils were rapidly recruited to the peritoneum after ATP injection. In addition, the effects on cytokine and chemokine secretion and neutrophil recruitment were markedly attenuated by the pre-administration of the caspase-1 inhibitor Ac-YVAD-cho. Ac-YVAD-cho also significantly attenuated the protective effect of ATP against bacterial infection. In the present study, we demonstrated a protective role for ATP during bacterial infection and this effect was related to NLRP3 inflammasome activation. Together, these results suggest a role for ATP in initiating the immune response in hosts suffering from infections.
已经证实三磷酸腺苷（ATP）可以激活 NLRP3 炎性小体。然而，细胞外 ATP 对 NLRP3 炎性小体激活的生理作用尚未得到研究。在本研究中，我们发现细菌感染过程中确实会释放 ATP。通过使用鼠腹膜炎模型，我们还发现 ATP 促进了小鼠对抗细菌感染的能力。ATP 诱导体外培养的鼠骨髓来源巨噬细胞分泌 IL-1β 和趋化因子。此外，腹腔内注射 ATP 可提高小鼠腹腔灌洗液中 IL-1β 和趋化因子的水平。ATP 注射后，中性粒细胞迅速募集到腹膜。此外，用半胱天冬酶-1 抑制剂 Ac-YVAD-cho 预处理可显著减弱细胞因子和趋化因子分泌以及中性粒细胞募集的作用。Ac-YVAD-cho 还显著减弱了 ATP 对细菌感染的保护作用。在本研究中，我们证明了 ATP 在细菌感染过程中的保护作用，这种作用与 NLRP3 炎性小体的激活有关。总之，这些结果表明 ATP 在宿主感染时启动免疫反应中发挥作用。
