Expression and function of adenosine receptors in human dendritic cells

Dendritic cells (DCs) are specialized antigen‐presenting cells characterized by their ability to migrate into target sites, process antigens, and activate naive T cells. In this study, we analyzed the biological activity and intracellular signaling of adenosine by using reverse transcriptase‐polymerase chain reaction assays to investigate mRNA expression of A1,A2a and A3 adenosine receptors in immature and mature human DCs. Functional experiments on adenosine stimulation showed chemotaxis, intracellular calcium transients, and actin polymerization, but no activation of adenylate cyclase in immature DCs. Experiments with receptor isotype‐selective agonists and antagonists as well as pertussis toxin revealed that chemotaxis, calcium transients, and actin polymerization were mediated via Gi‐or G0‐protein‐coupled A1 and A3 receptors. Maturation of DCs induced by lipopolysaccharide (LPS) resulted in down‐regulation of A1 and A3 receptor mRNAs, although A2a receptor mRNA was still expressed. However, in LPS‐differentiated DCs, adenosine and an A2a receptor agonist stimulated adenylate cyclase activity, enhanced intracellular cAMP levels, and inhibited in‐terleukin 12 (IL‐12) production. These effects could be completely prevented by pretreatment with A2 receptor antagonist. These findings strongly suggest that adenosine has important but distinct biological effects in DCs activity as a chemotaxin for immature DCs and as a modulator of IL‐12 production in mature DCs. These effects can be explained by differential expression of adenosine receptor subtypes.