PMID- 11160202
OWN - NLM
STAT- MEDLINE
DCOM- 20010419
LR  - 20220317
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 166
IP  - 3
DP  - 2001 Feb 1
TI  - Extracellular ATP induces a distorted maturation of dendritic cells and inhibits 
      their capacity to initiate Th1 responses.
PG  - 1611-7
AB  - Dendritic cells (DCs) express functional purinergic receptors, but the effects of 
      purine nucleotides on DC functions have been marginally investigated. In this 
      study, we report on the ability of micromolar concentrations of ATP to affect the 
      maturation and Ag-presenting function of monocyte-derived DCs in vitro. Chronic 
      stimulation (24 h) of DCs with low, noncytotoxic ATP doses increased membrane 
      expression of CD54, CD80, CD86, and CD83, slightly reduced the endocytic activity 
      of DCs, and augmented their capacity to promote proliferation of allogeneic naive 
      T lymphocytes. Moreover, ATP enhanced LPS- and soluble CD40 ligand-induced CD54, 
      CD86, and CD83 expression. On the other hand, ATP markedly and dose-dependently 
      inhibited LPS- and soluble CD40 ligand-dependent production of IL-1alpha, 
      IL-1beta, TNF-alpha, IL-6, and IL-12, whereas IL-1 receptor antagonist and IL-10 
      production was not affected. As a result, T cell lines generated from allogeneic 
      naive CD45RA(+) T cells primed with DCs matured in the presence of ATP produced 
      lower amounts of IFN-gamma and higher levels of IL-4, IL-5, and IL-10 compared 
      with T cell lines obtained with LPS-stimulated DCs. ATP inhibition of TNF-alpha 
      and IL-12 production by mature DCs was not mediated by PGs or elevation of 
      intracellular cAMP and did not require ATP degradation. The inability of UTP and 
      the similar potency of ADP to reproduce ATP effects indicated that ATP could 
      function through the P2X receptor family. These results suggest that 
      extracellular ATP may serve as an important regulatory signal to dampen IL-12 
      production by DCs and thus prevent exaggerated and harmful immune responses.
FAU - la Sala, A
AU  - la Sala A
AD  - Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, Istituto di 
      Ricovero e Cura a Carattere Scientifico, Rome, Italy. alasala@idi.it
FAU - Ferrari, D
AU  - Ferrari D
FAU - Corinti, S
AU  - Corinti S
FAU - Cavani, A
AU  - Cavani A
FAU - Di Virgilio, F
AU  - Di Virgilio F
FAU - Girolomoni, G
AU  - Girolomoni G
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Prostaglandins)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Adenosine Triphosphate/*immunology/metabolism/*pharmacology
MH  - Cell Differentiation/drug effects/immunology
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Cytokines/antagonists & inhibitors/biosynthesis
MH  - Dendritic Cells/drug effects/*immunology/metabolism/pathology
MH  - Dose-Response Relationship, Immunologic
MH  - Extracellular Space/*immunology/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Immunosuppressive Agents/*pharmacology
MH  - Inflammation/immunology
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-12/antagonists & inhibitors/biosynthesis/metabolism
MH  - Intracellular Fluid/metabolism
MH  - Prostaglandins/physiology
MH  - Receptors, Interleukin-1/biosynthesis
MH  - Th1 Cells/drug effects/*immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism
EDAT- 2001/02/13 11:00
MHDA- 2001/04/21 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/04/21 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - 10.4049/jimmunol.166.3.1611 [doi]
PST - ppublish
SO  - J Immunol. 2001 Feb 1;166(3):1611-7. doi: 10.4049/jimmunol.166.3.1611.