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ATP Release Guides Neutrophil Chemotaxis via P2Y2 and A3 Receptors
Yu Chen,1*Ross Corriden,1,2*Yoshiaki Inoue,1Linda Yip,1Naoyuki Hashiguchi,1Annelies Zinkernagel,4Victor Nizet,4Paul A. Insel,2,3Wolfgang G. Junger1
Cells must amplify external signals to orient and migrate inchemotactic gradient fields. We find that human neutrophilsrelease adenosine triphosphate (ATP) from the leading edge ofthe cell surface to amplify chemotactic signals and direct cellorientation by feedback through P2Y2 nucleotide receptors. Neutrophilsrapidly hydrolyze released ATP to adenosine that then acts viaA3-type adenosine receptors, which are recruited to the leadingedge, to promote cell migration. Thus, ATP release and autocrinefeedback 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.
To whom correspondence should be addressed. E-mail: wjunger{at}ucsd.edu
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