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Expression and function of adenosine receptors in human dendritic cells
Author(s) -
PANTHER ELISABETH,
IDZKO MARCO,
HEROUY YARED,
RHEINEN HENRIETTE,
GEBICKEHAERTER PETER J.,
MROWIETZ ULRICH,
DICHMANN STEFAN,
NORGAUER JOHANNES
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0169com
Subject(s) - adenosine , microbiology and biotechnology , adenosine a2b receptor , adenosine a3 receptor , adenosine receptor , receptor , purinergic signalling , chemotaxis , biology , chemistry , adenosine a1 receptor , agonist , biochemistry
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 A 1 ,A 2a and A 3 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 G i ‐or G 0 ‐protein‐coupled A 1 and A 3 receptors. Maturation of DCs induced by lipopolysaccharide (LPS) resulted in down‐regulation of A 1 and A 3 receptor mRNAs, although A 2a receptor mRNA was still expressed. However, in LPS‐differentiated DCs, adenosine and an A 2a 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 A 2 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.