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Title: ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling.
Authors: Schnurr, Max;Toy, Tracey;Stoitzner, Patrizia;Cameron, Paul;Shin, Amanda;Beecroft, Tina;Davis, Ian D;Cebon, Jonathan S;Maraskovsky, Eugene
Affiliation: Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Austin, Australia.
Issue Date: 20-Mar-2003
Citation: Blood 2003; 102(2): 613-20
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-derived DCs (MoDCs) and CD1a+ dermal DCs to gradients of ATP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y11R. On maturation, MoDCs down-regulated P2Y11R 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 P2Y11R, calcium-flux studies showed that blood DC types were unresponsive to P2Y11R 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.
Internal ID Number: 12649135
DOI: 10.1182/blood-2002-12-3745
Type: Journal Article
Subjects: Adenosine Triphosphate.pharmacology
Antigens, CD1.analysis
Calcium Signaling.drug effects
Chemotaxis.drug effects
Dendritic Cells.classification.drug effects.physiology
Depression, Chemical
Dose-Response Relationship, Drug
Drug Resistance
Melanoma.blood.drug therapy.immunology
Membrane Proteins.pharmacology.therapeutic use
Phosphatidylinositol Diacylglycerol-Lyase
RNA, Messenger.biosynthesis.genetics
Receptors, Interleukin-3.analysis
Receptors, Purinergic P2.biosynthesis.genetics.physiology
Signal Transduction.drug effects
Tumor Necrosis Factor-alpha.pharmacology
Type C Phospholipases.physiology
Appears in Collections:Journal articles

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