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Purinergic signaling: a fundamental mechanism in neutrophil activation.

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 Fcgamma, interleukin-8, C5a complement, and leukotriene B(4) 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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC4209711 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Purinergic signaling: a fundamental mechanism in neutrophil activation.

Chen Yu Y Yao Yongli Y Sumi Yuka Y Li Andrew A To Uyen Kim UK Elkhal Abdallah A Inoue Yoshiaki Y Woehrle Tobias T Zhang Qin Q Hauser Carl C Junger Wolfgang G WG

Science signaling 20100608 125

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 Fcgamma, interleukin-8, C5a complement, and leukotriene B(4) receptors. Stimulation of the formyl peptide receptor (FPR) led to ATP release through pannexin-1 (panx1) hemichannels, and FPRs colocalized with P2Y2 nucleotide re ...[more]

PMID: 20530802

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Autocrine stimulation of P2Y1 receptors is part of the purinergic signaling mechanism that regulates T cell activation.

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