Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates neutrophil chemotaxis by hydrolyzing released ATP to adenosine.
Polymorphonuclear neutrophils release ATP in response to stimulation by chemoattractants, such as the peptide N-formyl-methionyl-leucyl-phenylalanine. Released ATP and the hydrolytic product adenosine regulate chemotaxis of neutrophils by sequentially activating purinergic nucleotide and adenosine receptors, respectively. Here we show that that ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1, CD39) is a critical enzyme for hydrolysis of released ATP by neutrophils and for cell migration in response to multiple agonists (N-formyl-methionyl-leucyl-phenylalanine, interleukin-8, and C5a). Upon stimulation of human neutrophils or differentiated HL-60 cells in a chemotactic gradient, E-NTPDase1 tightly associates with the leading edge of polarized cells during chemotaxis. Inhibition of E-NTPDase1 reduces the migration speed of neutrophils but not their ability to detect the orientation of the gradient field. Studies of neutrophils from E-NTPDase1 knock-out mice reveal similar impairments of chemotaxis in vitro and in vivo. Thus, E-NTPDase1 plays an important role in regulating neutrophil chemotaxis by facilitating the hydrolysis of extracellular ATP.
Corriden
Ross
R
Department of Surgery, University of California San Diego, La Jolla, California 92093, USA.
Chen
Yu
Y
Inoue
Yoshiaki
Y
Beldi
Guido
G
Robson
Simon C
SC
Insel
Paul A
PA
Junger
Wolfgang G
WG
D000241:Adenosine / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry*; D001081:Apyrase / Q000737:chemistry*; D002454:Cell Differentiation; D002465:Cell Movement; D002633:Chemotaxis; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D015703:Antigens, CD; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine