Novel cell death program leads to neutrophil extracellular traps.
Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.
Fuchs
Tobias A
TA
Department for Cellular Microbiology, Max-Planck Institute for Infection Biology, 10117 Berlin, Germany.
Abed
Ulrike
U
Goosmann
Christian
C
Hurwitz
Robert
R
Schulze
Ilka
I
Wahn
Volker
V
Weinrauch
Yvette
Y
Brinkmann
Volker
V
Zychlinsky
Arturo
A
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006105:Granulomatous Disease, Chronic / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007113:Immunity, Innate / Q000502:physiology*; D019272:Leukocyte Elastase / Q000378:metabolism; D008854:Microscopy, Electron; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D009861:Onium Compounds / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure; D019014:fas Receptor / Q000276:immunology
D000906:Antibodies; D002843:Chromatin; D004791:Enzyme Inhibitors; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D019014:fas Receptor; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D002374:Catalase; D019255:NADPH Oxidases; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate