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| ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y(11) receptor signaling |
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| Author(s): Schnurr M, Toy T, Stoitzner P, Cameron P, Shin A, Beecroft T, Davis ID, Cebon J, Maraskovsky E |
| Source: BLOOD Volume: 102 Issue: 2 Pages: 613-620 Published: JUL 15 2003 |
| Times Cited: 53 References: 35 |
| Abstract: Dendritic cells (DCs) are specialized antigen-presenting cells residing in tissues, from which they take up antigen. Activated DCs migrate through chemokine gradients from sites of inflammation to lymph nodes to stimulate T cells. At sites of inflammation, nucleotides, such as adenosine triphosphate (ATP), are released by activated or dying cells and can function as signaling molecules through P2 receptors (P2Rs). We investigated P2R expression in different DC populations and the effect of nucleotides on chemokine-directed migration. Exposure of monocyte-deirived DCs (MoDCs) and CD1a(+) dermal DCs to gradients of ATIP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y(11)R. On maturation, MoDCs down-regulated P2Y(11)R expression and were less sensitive to ATP-mediated inhibition of migration. In contrast, ATP did not inhibit the migration of CD1c(+) peripheral blood (PB) DCs or Interleukin-3 receptor-positive (IL-3R(+)) plasmacytoid DCs. Although all 4 DC populations expressed mRNA for P2Y(11)R, calcium-flux studies showed that blood DC types were unresponsive to P2Y(11)R agonists. In conclusion, DCs use distinct subtypes of P2R. The formation of ATP gradients at sites of inflammation may transiently inhibit the migration of local DCs, thus prolonging the time of antigen encounter. P2R inhibition may represent a new strategy to improve the migration of antigen-loaded DCs from the vaccination site to lymph nodes. (C) 2003 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Schnurr, M (reprint author), Austin & Repatriat Med Ctr, Ludwig Inst Oncol Unit, Studley Rd, Heidelberg, Vic 3084 Australia |
Addresses:
1. Austin & Repatriat Med Ctr, Melbourne Tumour Biol Branch, Ludwig Inst Canc Res, Heidelberg, Vic Australia
2. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052 Australia
3. Innsbruck Univ, Dept Dermatol, A-6020 Innsbruck, Austria |
| Publisher: AMER SOC HEMATOLOGY, 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA |
| Subject Category: Hematology |
| IDS Number: 699XY |
| ISSN: 0006-4971 |
| DOI: 10.1182/blood-2002-12-3745 |
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