PT  - JOURNAL ARTICLE
AU  - Chen, Yu
AU  - Yao, Yongli
AU  - Sumi, Yuka
AU  - Li, Andrew
AU  - To, Uyen Kim
AU  - Elkhal, Abdallah
AU  - Inoue, Yoshiaki
AU  - Woehrle, Tobias
AU  - Zhang, Qin
AU  - Hauser, Carl
AU  - Junger, Wolfgang G.
TI  - Purinergic Signaling: A Fundamental Mechanism in Neutrophil Activation
AID  - 10.1126/scisignal.2000549
DP  - 2010 Jun 08
TA  - Science Signaling
PG  - ra45--ra45
VI  - 3
IP  - 125
4099  - http://stke.sciencemag.org/content/3/125/ra45.short
4100  - http://stke.sciencemag.org/content/3/125/ra45.full
SO  - Sci. Signal.2010 Jun 08; 3
AB  - 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 Fcγ, 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.