Characterization of the biological aktivities of uridine diphosphate in human dendritic cells: Influence on chemotaxis and CXCL8 release

Uridine nucleotides are endogenous nucleotides which are released into the extracellular space from mechanical stressed endothelial and epithelial cells as well as lipopolysaccharide (lps)-stimulated monocytes. Here, we studied the biological activity of the selective purinoreceptor P2Y6 (P2YR6) agonist uridine diphosphate (UDP) as well as the P2YR2- and P2YR4-activating uridine triphosphate (UTP) on human dendritic cells (DC). Immature DC have the ability to migrate from blood to peripheral target sites where they sense for dangerous signals and capture potential antigens. Mature DC induce innate immune responses and migrate from peripheral tissues to secondary lymphoid organs in order to activate naive T cells and initiate adaptive immunity. Here we could show that UDP and UTP stimulated Ca2+ transients, actin polymerization, and chemotaxis in immature DC. Experiments with pertussis toxin, receptor antagonists, and desensitization studies suggested that these uridine nucleotides activities were mediated by different G protein-coupled receptors. During maturation, DC lost their ability to respond towards UDP and UTP with these activities, while UDP, but not UTP, stimulated now the release of the CXC-chemokine 8 (CXCL8) in a reactive blue sensitive manner. In aggregate, our study indicates that UDP stimulates different signaling pathways in immature and mature DC in order to favor the accumulation of immature DC and to augment the capacity to secrete CXCL8 in mature DC.