Extracellular uridine nucleotides initiate cytokine production by murine dendritic cells

While it is recognized that activated dendritic cells perform their immune functions with greater efficacy, it is not altogether clear what factors ar e responsible for such activation. Recent evidence points to an important r ole for extracellular nucleotides in the modulation of leukocyte function. In the present study we investigated the ability of extracellular nucleotid es to activate CD11c(+) murine dendritic cells. Mobilization of intracellul ar calcium was observed following treatment of these cells with UTP or UDP, but not ATP. Furthermore, this nucleotide receptor was pertussis toxin-sen sitive, suggesting the presence of a P2Y nucleotide receptor. Such receptor s were not present on murine peritoneal macrophages or on CD11c-negative le ukocyte populations. Importantly, activation of these P2Y nucleotide recept ors on dendritic cells provided a potent stimulus for cytokine mRNA express ion and secretion. Thus, expression of a P2Y nucleotide receptor on CD11c() dendritic cells functions to mobilize intracellular calcium and to induce cytokine production. (C) 1999 Academic Press.