ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors.
Cells must amplify external signals to orient and migrate in chemotactic gradient fields. We find that human neutrophils release adenosine triphosphate (ATP) from the leading edge of the cell surface to amplify chemotactic signals and direct cell orientation by feedback through P2Y2 nucleotide receptors. Neutrophils rapidly hydrolyze released ATP to adenosine that then acts via A3-type adenosine receptors, which are recruited to the leading edge, to promote cell migration. Thus, ATP release and autocrine feedback through P2Y2 and A3 receptors provide signal amplification, controlling gradient sensing and migration of neutrophils.
Chen
Yu
Y
Department of Surgery, University of California San Diego, San Diego, CA 92103, USA.
Corriden
Ross
R
Inoue
Yoshiaki
Y
Yip
Linda
L
Hashiguchi
Naoyuki
N
Zinkernagel
Annelies
A
Nizet
Victor
V
Insel
Paul A
PA
Junger
Wolfgang G
WG
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019898:Autocrine Communication; D002462:Cell Membrane / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction; D013498:Suramin / Q000494:pharmacology
D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; C546385:P2RY2 protein, human; C546386:P2ry2 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D000255:Adenosine Triphosphate; D000241:Adenosine