Adenosine slows migration of dendritic cells but does not affect other aspects of dendritic cell maturation.
We report the induction and reduction of adenosine receptor A2a and A3 mRNAs, respectively, during maturation of human monocyte-derived dendritic cells. Adenosine, an immunomodulatory molecule, is unstable in vitro; therefore we tested a stable agonist, 5'-(N-ethylcarboxamido)-adenosine, to explore the effect of adenosine receptor activation on dendritic cell function. We clearly show that adenosine receptor engagement affects the migratory activity of dendritic cells in three distinct settings. In human skin explant culture experiments the emigration of epidermal and dermal dendritic cells was diminished by the addition of 5'-(N-ethylcarboxamido)-adenosine. In a murine contact hypersensitivity assay 5'-(N-ethylcarboxamido)-adenosine caused a reduction in the numbers of epidermal and dermal dendritic cells arriving in the draining lymph node. In a chemotaxis assay of human dendritic cells in response to macrophage inflammatory protein 3beta (MIP-3beta)/CCL19, adenosine caused a delay in transmigration. Expression of a number of molecules involved in dendritic cell migration (CCR5, MIP-3beta/CCL19, and MDR-1) was reduced. Importantly, all other features of dendritic cells tested--phenotype, antigen uptake, cytokine production, T cell activation, and the T cell subset induction--remained unchanged. Dendritic cells carry antigens from the periphery to secondary lymphoid organs, where initiation of immune responses occurs. Increased adenosine release may modulate immune responses by delaying the encounter of antigen-loaded dendritic cells with T cells.
Hofer
Susanne
S
Department of Dermatology, University of Innsbruck, Innsbruck, Austria.
Ivarsson
Lennart
L
Stoitzner
Patrizia
P
Auffinger
Margit
M
Rainer
Christian
C
Romani
Nikolaus
N
Heufler
Christine
C
D000241:Adenosine / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000494:pharmacology; D046508:Culture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology; D008198:Lymph Nodes / Q000502:physiology; D010641:Phenotype; D010853:Picryl Chloride / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012867:Skin / Q000166:cytology
C515460:CCL19 protein, human; D054415:Chemokine CCL19; D019742:Chemokines, CC; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine; D010853:Picryl Chloride