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Science 15 December 2006:
Vol. 314. no. 5806, pp. 1792 - 1795
DOI: 10.1126/science.1132559
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Reports

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}

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}ucsd.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)