Purinergic signaling: a fundamental mechanism in neutrophil activation.
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.
Chen
Yu
Y
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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
D000255:Adenosine Triphosphate / Q000378:metabolism; D006801:Humans; D018375:Neutrophil Activation; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate