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Science 314 (5806): 1792-1795

Copyright © 2006 by the American Association for the Advancement of Science

ATP Release Guides Neutrophil Chemotaxis via P2Y2 and A3 Receptors

Yu Chen,1* Ross Corriden,1,2* Yoshiaki Inoue,1 Linda Yip,1 Naoyuki Hashiguchi,1 Annelies Zinkernagel,4 Victor Nizet,4 Paul A. Insel,2,3 Wolfgang G. Junger1{dagger}

Abstract: 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.

1 Department of Surgery, University of California San Diego, San Diego, CA 92103, USA.
2 Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
3 Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
4 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: wjunger{at}

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K. R. Vaughan, L. Stokes, L. R. Prince, H. M. Marriott, S. Meis, M. U. Kassack, C. D. Bingle, I. Sabroe, A. Surprenant, and M. K. B. Whyte (2007)
J. Immunol. 179, 8544-8553
   Abstract »    Full Text »    PDF »
G{alpha}(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration.
S. Taboubi, J. Milanini, E. Delamarre, F. Parat, F. Garrouste, G. Pommier, J. Takasaki, J.-C. Hubaud, H. Kovacic, and M. Lehmann (2007)
FASEB J 21, 4047-4058
   Abstract »    Full Text »    PDF »
Inhibition of Tumor Angiogenesis by Targeting Endothelial Surface ATP Synthase with Sangivamycin.
Y. Komi, O. Ohno, Y. Suzuki, M. Shimamura, K. Shimokado, K. Umezawa, and S. Kojima (2007)
Jpn. J. Clin. Oncol. 37, 867-873
   Abstract »    Full Text »    PDF »
Purinergic P2Y2 Receptors Induce Increased MCP-1/CCL2 Synthesis and Release from Rat Alveolar and Peritoneal Macrophages.
L. Stokes and A. Surprenant (2007)
J. Immunol. 179, 6016-6023
   Abstract »    Full Text »    PDF »
Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption.
T. Rieg, R. A. Bundey, Y. Chen, G. Deschenes, W. Junger, P. A. Insel, and V. Vallon (2007)
FASEB J 21, 3717-3726
   Abstract »    Full Text »    PDF »
Ca2+ influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophages.
J. H. Evans and J. J. Falke (2007)
PNAS 104, 16176-16181
   Abstract »    Full Text »    PDF »
Isothiocyanate Inhibits Restitution and Wound Repair after Injury in the Stomach: Ex Vivo and in Vitro Studies.
R. Ragasa, E. Nakamura, L. Marrone, S. Yanaka, S. Hayashi, K. Takeuchi, and S. J. Hagen (2007)
J. Pharmacol. Exp. Ther. 323, 1-9
   Abstract »    Full Text »    PDF »
A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells.
R. Corriden, P. A. Insel, and W. G. Junger (2007)
Am J Physiol Cell Physiol 293, C1420-C1425
   Abstract »    Full Text »    PDF »
The P2Y2 nucleotide receptor requires interaction with {alpha}v integrins to access and activate G12.
Z. Liao, C. I. Seye, G. A. Weisman, and L. Erb (2007)
J. Cell Sci. 120, 1654-1662
   Abstract »    Full Text »    PDF »
Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo.
F. Kukulski, F. Ben Yebdri, J. Lefebvre, M. Warny, P. A. Tessier, and J. Sevigny (2007)
J. Leukoc. Biol. 81, 1269-1275
   Abstract »    Full Text »    PDF »
CELL BIOLOGY: Purinergic Chemotaxis.
J. Linden (2006)
Science 314, 1689-1690
   Abstract »    Full Text »    PDF »

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