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 are responsible for such activation. Recent evidence points to an important role for extracellular nucleotides in the modulation of leukocyte function. In the present study we investigated the ability of extracellular nucleotides to activate CD11c(+) murine dendritic cells. Mobilization of intracellular calcium was observed following treatment of these cells with UTP or UDP, but not ATP. Furthermore, this nucleotide receptor was pertussis toxin-sensitive, suggesting the presence of a P2Y nucleotide receptor. Such receptors were not present on murine peritoneal macrophages or on CD11c-negative leukocyte populations. Importantly, activation of these P2Y nucleotide receptors on dendritic cells provided a potent stimulus for cytokine mRNA expression and secretion. Thus, expression of a P2Y nucleotide receptor on CD11c(+) dendritic cells functions to mobilize intracellular calcium and to induce cytokine production.
Marriott
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Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
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D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014500:Uracil Nucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000227:Adenine Nucleotides; D007378:Interleukins; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014500:Uracil Nucleotides; D010566:Virulence Factors, Bordetella; D013498:Suramin; D019284:Thapsigargin; D037342:Pertussis Toxin; D002118:Calcium