Extracellular ATP is a potent signaling molecule in the activation ofthe Japanese flounder (

摘要

Innate immunity is the first line of defense against pathogen infections.Extracellular ATP (eATP) is one of the most studied danger-associated molecularpattern molecules that can activate host innate immune responses through bindingwith and activating purinergic receptors on the plasma membrane. The detailedactions of eATP on fish innate immunity, however, remain poorly understood. Inthis study, we investigated bacterial pathogen-induced ATP release in headkidney cells of the Japanese flounder Paralichthys olivaceus.We also examined the actions of eATP on pro-inflammatory cytokine andimmune-related gene expression, the activity of induced NO synthase (iNOS), andthe production of reactive oxygen species (ROS) and NO in Japanese flounderimmune cells. We demonstrate that ATP is dynamically released from Japaneseflounder head kidney cells into the extracellular milieu during immune challengeby formalin-inactivated Edwardsiella tarda and Vibrioanguillarum. In addition, we show that eATP administration resultsin profound up-regulation of pro-inflammatory cytokine gene expression, iNOSactivity, and inflammatory mediator production, including ROS and NO, inJapanese flounder immune cells. Altogether, our findings demonstrate that eATPis a potent signaling molecule for the activation of innate immune responses infish.