Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps.
Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.
Yousefi
S
S
Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland. shida.yousefi@pki.unibe.ch
Mihalache
C
C
Kozlowski
E
E
Schmid
I
I
Simon
H U
HU
D017209:Apoptosis; D015936:Complement C5a / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor