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Extracellular adenosine modulates neutrophil host‐pathogen interactions via activation of the A3‐adenosine receptor
Author(s) -
Corriden Ross,
Briddon Steve,
Hill Stephen J,
Nizet Victor
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.888.6
Subject(s) - chemotaxis , microbiology and biotechnology , adenosine , neutrophil extracellular traps , innate immune system , purinergic signalling , adenosine receptor , extracellular , phagocytosis , receptor , biology , chemistry , inflammation , immunology , biochemistry , agonist
Extracellular nucleotides/nucleosides are important mediators of immune cell function that activate a diverse array of membrane receptors. Of these, the A3‐adenosine receptor (A3AR) stands out as a key regulator of neutrophil behavior. Here, we use a fluorescent A3AR ligand in conjunction with flow cytometry and confocal microscopy to show that endogenous A3ARs aggregate in highly polarized plaque‐like microdomains that modulate human neutrophil chemotaxis. In addition to regulating chemotaxis, A3ARs promote the formation of membrane projections that enable neutrophils to tether and “reel in” bacteria to the cell membrane. Exposure of neutrophils to adenosine, particularly in the presence of the A2a‐selective inhibitor ZM 241385, enhances their ability to kill Staphylococcus aureus and phagocytose Staphylococcus aureus bioparticles. Our results reveal new properties of human neutrophils and identify the A3AR as a potential target for modulating the innate immune function of these cells.