title: Human monocytes respond to extracellular cAMP through A2A and A2B adenosine receptors.
abstract: In this study, we test the hypothesis that cAMP, acting as an extracellular mediator, affects the physiology and function of human myeloid cells. The cAMP is a second messenger recognized as a universal regulator of several cellular functions in different organisms. Many studies have shown that extracellular cAMP exerts regulatory functions, acting as first mediator in multiple tissues. However, the impact of extracellular cAMP on cells of the immune system has not been fully investigated. We found that human monocytes exposed to extracellular cAMP exhibit higher expression of CD14 and lower amount of MHC class I and class II molecules. When cAMP-treated monocytes are exposed to proinflammatory stimuli, they exhibit an increased production of IL-6 and IL-10 and a lower amount of TNF-α and IL-12 compared with control cells, resembling the features of the alternative-activated macrophages or M2 macrophages. In addition, we show that extracellular cAMP affects monocyte differentiation into DCs, promoting the induction of cells displaying an activated, macrophage-like phenotype with reduced capacity of polarized, naive CD4(+) T cells into IFN-γ-producing lymphocytes compared with control cells. The effects of extracellular cAMP on monocytes are mediated by CD73 ecto-5'-nucleotidase and A2A and A2B adenosine receptors, as selective antagonists could reverse its effects. Of note, the expression of CD73 molecules has been found on the membrane of a small population of CD14(+)CD16(+) monocytes. These findings suggest that an extracellular cAMP-adenosine pathway is active in cells of the immune systems.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and.
authors.forename: Ester
authors.initials: E
authors.lastname: Sciaraffia
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and.
authors.forename: Antonella
authors.initials: A
authors.lastname: Riccomi
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Lindstedt
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gesa
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and Animal Breeding Department, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cirelli
authors.affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy; and.
authors.forename: Mario
authors.initials: M
authors.lastname: Patrizio
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: De Magistris
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, and vendetti@iss.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vendetti
mesh_terms: D015720:5'-Nucleotidase / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000276:immunology / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000242:Cyclic AMP; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: dendritic cells; ecto-5′-nucleotidases; macrophages