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Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Abstract

Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

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Abbreviations

cAMP:

Cyclic adenosine monophosphate

DCs:

Dendritic cells

ECP:

Eosinophil cationic protein

ERK:

Extracellular signal-regulated kinases

fMLP:

fMet-Leu-Phe receptor

HLMC:

Human lung mast cell

HMC:

Human mast cell

IP3 :

Inositol 1,4,5-triphosphate

LAD 2:

Leukocyte adhesion deficiency

LCL:

Lymphoblastoid cell lines

MIP-2:

Macrophage inflammatory protein-2

MoDCs:

Monocyte-derived dendritic cells

MSU:

Monosodium urate

E-NTPDase1:

Ecto-nucleoside triphosphate diphosphohydrolase 1

PLC:

Phospholipase C

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Acknowledgments

This work was supported by funding from The Research Foundation Flanders (FWO); research project Nr. G.0641.10 to KVC, and a Concerted Research Action project (01G01009) from the Special Research Fund of Ghent University. The figures were generated using Servier Medical Art’s Powerpoint image banks available at www.servier.com.

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Correspondence to Koen Van Crombruggen.

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Fenila Jacob and Koen Van Crombruggen contributed equally to this work

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Jacob, F., Novo, C.P., Bachert, C. et al. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signalling 9, 285–306 (2013). https://doi.org/10.1007/s11302-013-9357-4

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  • DOI: https://doi.org/10.1007/s11302-013-9357-4

Keywords

  • ATP
  • Extracellular nucleotides
  • P2 receptors
  • Inflammatory cells
  • Regulation of immune responses