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Sci. Signal., 8 June 2010
Vol. 3, Issue 125, p. ra45
[DOI: 10.1126/scisignal.2000549]

RESEARCH ARTICLES

Purinergic Signaling: A Fundamental Mechanism in Neutrophil Activation

Yu Chen1, Yongli Yao1, Yuka Sumi1, Andrew Li1, Uyen Kim To1, Abdallah Elkhal1, Yoshiaki Inoue1, Tobias Woehrle1, Qin Zhang1, Carl Hauser1, and Wolfgang G. Junger1,2*

1 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
2 Ludwig Boltzmann Institute for Experimental Traumatology, Vienna A-1200, Austria.

Abstract: Efficient activation of neutrophils is a key requirement for effective immune responses. We found that neutrophils released cellular adenosine triphosphate (ATP) in response to exogenous stimuli such as formylated bacterial peptides and inflammatory mediators that activated Fc{gamma}, interleukin-8, C5a complement, and leukotriene B4 receptors. Stimulation of the formyl peptide receptor (FPR) led to ATP release through pannexin-1 (panx1) hemichannels, and FPRs colocalized with P2Y2 nucleotide receptors on the cell surface to form a purinergic signaling system that facilitated neutrophil activation. Disruption of this purinergic signaling system by inhibiting or silencing panx1 hemichannels or P2Y2 receptors blocked neutrophil activation and impaired innate host responses to bacterial infection. Thus, purinergic signaling is a fundamental mechanism required for neutrophil activation and immune defense.

* To whom correspondence should be addressed. E-mail: wjunger{at}bidmc.harvard.edu

Citation: Y. Chen, Y. Yao, Y. Sumi, A. Li, U. K. To, A. Elkhal, Y. Inoue, T. Woehrle, Q. Zhang, C. Hauser, W. G. Junger, Purinergic Signaling: A Fundamental Mechanism in Neutrophil Activation. Sci. Signal. 3, ra45 (2010).

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