title: Dendritic cells exposed to extracellular adenosine triphosphate acquire the migratory properties of mature cells and show a reduced capacity to attract type 1 T lymphocytes.
abstract: We previously reported that chronic stimulation with low, noncytotoxic doses of extracellular adenosine triphosphate (ATP) induced a distorted maturation of dendritic cells (DCs) and impaired their capacity to initiate T-helper (Th) 1 responses in vitro. Here, we examined the effects of ATP on chemokine-receptor expression and chemokine production by DCs. ATP strongly induced expression of CXC chemokine receptor 4 on both immature and lipopolysaccharide (LPS)-stimulated DCs and slightly up-regulated CC chemokine receptor (CCR) 7 on both DC types. In contrast, ATP reduced CCR5 expression on immature DCs. These effects were confirmed at both the messenger RNA and protein levels and were not produced by uridine triphosphate (UTP). Consistent with the changed receptor expression, ATP increased migration and intracellular calcium of immature and mature DCs to stromal-derived factor 1 (CXC ligand [CXCL] 12) and macrophage inflammatory protein [MIP] 3 beta (CC ligand [CCL] 19), whereas responses to MIP-1 beta (CCL4) were reduced. DCs are an important source of chemokines influencing recruitment of distinct T-lymphocyte subsets. ATP, but not UTP, significantly reduced LPS-induced production of interferon-inducible protein 10 (CXCL10) and regulated upon activation, normal T-cell expressed and secreted chemokine (CCL5); increased secretion of macrophage-derived chemokine (CCL22); and did not change production of thymus and activation-regulated chemokine (CCL17). Consistent with these findings, supernatants from ATP-treated mature DCs attracted Th1 and T-cytotoxic 1 cells less efficiently, whereas migration of Th2 and T cytotoxic 2 cells was not affected. Our data suggest that ATP provides a signal for enhanced lymph node localization of DCs but that it may, at the same time, diminish the capacity of DCs to amplify type 1 immune responses.
authors.affiliation: Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: la Sala
authors.forename: Silvia
authors.initials: S
authors.lastname: Sebastiani
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrari
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.forename: Johannes
authors.initials: J
authors.lastname: Norgauer
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D054422:Chemokine CCL22; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis / Q000378:metabolism; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013601:T-Lymphocytes
chemical_list: C515482:CCL22 protein, human; C515370:CCR7 protein, human; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D000255:Adenosine Triphosphate