Granstein Richard D, Ding Wanhong, Huang Jing, Holzer Aton, Gallo Richard L, Di Nardo Anna, Wagner John A
Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.
J Immunol. 2005 Jun 15;174(12):7725-31. doi: 10.4049/jimmunol.174.12.7725.
Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein-coupled P2YRs. In this study we report that intradermal administration of ATPgammaS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice. Furthermore, ATPgammaS enhanced the induction of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced the Ag-presenting function of Langerhans cells (LCs) in vitro. Exposure of a LC-like cell line to ATPgammaS in the presence of LPS and GM-CSF augmented the induction of I-A, CD80, CD86, IL-1beta, and IL-12 p40 while inhibiting the expression of IL-10, suggesting that the immunostimulatory activities of purinergic agonists in the skin are mediated at least in part by P2Rs on APCs. In this regard, an LC-like cell line was found to express mRNA for P2X(1), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(9), and P2Y(11) receptors. We suggest that ATP, when released after trauma or infection, may act as an endogenous adjuvant to enhance the immune response, and that P2 agonists may augment the efficacy of vaccines.
细胞外核苷酸可激活配体门控的P2XR离子通道和G蛋白偶联的P2YR。在本研究中，我们报告皮内注射ATPγS（一种抗水解的P2激动剂）可增强小鼠的接触性超敏反应。此外，ATPγS增强了小鼠对模型肿瘤疫苗的迟发型超敏反应的诱导，并在体外增强了朗格汉斯细胞（LC）的抗原呈递功能。在LPS和GM-CSF存在的情况下，将一种LC样细胞系暴露于ATPγS可增强I-A、CD80、CD86、IL-1β和IL-12 p40的诱导，同时抑制IL-10的表达，这表明嘌呤能激动剂在皮肤中的免疫刺激活性至少部分是由APC上的P2R介导的。在这方面，发现一种LC样细胞系表达P2X(1)、P2X(7)、P2Y(1)、P2Y(2)、P2Y(4)、P2Y(9)和P2Y(11)受体的mRNA。我们认为，ATP在创伤或感染后释放时，可能作为内源性佐剂增强免疫反应，并且P2激动剂可能增强疫苗的效力。
