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E‐NTPDase1 and alkaline phosphatase control chemotaxis of human neutrophils by generating adenosine from released ATP
Author(s) -
Corriden Ross,
Insel Paul A.,
Chen Yu,
Junger Wolfgang G.
Publication year - 2008
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.22.1_supplement.1179.3
Subject(s) - chemotaxis , adenosine , atp hydrolysis , chemistry , adenosine triphosphate , apyrase , purinergic signalling , extracellular , microbiology and biotechnology , biochemistry , phosphatase , purinergic receptor , alkaline phosphatase , atpase , adenosine receptor , receptor , enzyme , biology , agonist
Human polymorphonuclear neutrophils (PMN) release ATP in response to stimulation by chemoattractants. Released ATP and its product adenosine regulate chemotaxis by activating P2 and P1 receptors, respectively. Here we investigated the ecto‐ATPases that generate adenosine from released ATP. We find that ecto‐nucleoside‐triphosphate‐diphosphohydrolases 1 (E‐NTPDase1, CD39), which hydrolyses ATP to AMP, and alkaline phosphatase (ALP), which converts AMP to adenosine, are highly expressed in human PMN and that E‐NTPDase1 and ALP are recruited to the leading edge upon polarization of PMN in a chemotactic gradient. While E‐NTPDase1 is tightly associated with the leading edge, ALP remains more broadly distributed across the cell membrane. Inhibitors of E‐NTPDase1 reduced ATP hydrolysis by 60%, while inhibitors of ALP completely blocked the generation of adenosine. Inhibition of both enzymes significantly reduced the migration speed of PMN towards chemoattractant in a gradient field. Thus, E‐NTPDase1 and ALP play important roles in the control of PMN chemotaxis by generating extracellular adenosine from released ATP. (Supported by grants from NIGMS and DOD)