PMID- 12649135
OWN - NLM
STAT- MEDLINE
DCOM- 20030912
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 2
DP  - 2003 Jul 15
TI  - ATP gradients inhibit the migratory capacity of specific human dendritic cell 
      types: implications for P2Y11 receptor signaling.
PG  - 613-20
AB  - 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.
FAU - Schnurr, Max
AU  - Schnurr M
AD  - Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Austin, 
      Australia. max.schnurr@ludwig.edu.au
FAU - Toy, Tracey
AU  - Toy T
FAU - Stoitzner, Patrizia
AU  - Stoitzner P
FAU - Cameron, Paul
AU  - Cameron P
FAU - Shin, Amanda
AU  - Shin A
FAU - Beecroft, Tina
AU  - Beecroft T
FAU - Davis, Ian D
AU  - Davis ID
FAU - Cebon, Jonathan
AU  - Cebon J
FAU - Maraskovsky, Eugene
AU  - Maraskovsky E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030320
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD1)
RN  - 0 (CD1C protein, human)
RN  - 0 (Glycoproteins)
RN  - 0 (Interferon-alpha)
RN  - 0 (Membrane Proteins)
RN  - 0 (P2RY11 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-3)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (flt3 ligand protein)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 4.6.1.13 (Phosphatidylinositol Diacylglycerol-Lyase)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adenosine Triphosphate/*pharmacology
MH  - Antigens, CD1/analysis
MH  - Calcium Signaling/drug effects
MH  - Chemotaxis/*drug effects
MH  - Dendritic Cells/classification/*drug effects/physiology
MH  - Depression, Chemical
MH  - Dermis/cytology
MH  - Dinoprostone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance
MH  - Glycoproteins/analysis
MH  - Humans
MH  - Inflammation
MH  - Interferon-alpha/pharmacology
MH  - Melanoma/blood/drug therapy/immunology
MH  - Membrane Proteins/pharmacology/therapeutic use
MH  - Monocytes/cytology
MH  - Phosphatidylinositol Diacylglycerol-Lyase
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Interleukin-3/analysis
MH  - Receptors, Purinergic P2/biosynthesis/genetics/*physiology
MH  - Signal Transduction/*drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Type C Phospholipases/physiology
EDAT- 2003/03/22 04:00
MHDA- 2003/09/13 05:00
CRDT- 2003/03/22 04:00
PHST- 2003/03/22 04:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/03/22 04:00 [entrez]
AID - S0006-4971(20)44382-4 [pii]
AID - 10.1182/blood-2002-12-3745 [doi]
PST - ppublish
SO  - Blood. 2003 Jul 15;102(2):613-20. doi: 10.1182/blood-2002-12-3745. Epub 2003 Mar 
      20.