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Published online
doi:10.1083/jcb.200606027
The Journal of Cell Biology, Vol. 176, No. 2, 231-241
The Rockefeller University Press, 0021-9525 $30.00
© Fuchs et al.
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Article

Novel cell death program leads to neutrophil extracellular traps



Tobias A. Fuchs1,5, Ulrike Abed1,2, Christian Goosmann1,2, Robert Hurwitz3, Ilka Schulze4, Volker Wahn4, Yvette Weinrauch5, Volker Brinkmann2, and Arturo Zychlinsky1

1 Department for Cellular Microbiology, 2 Microscopy Core Facility, and 3 Protein Purification Core Facility, Max-Planck Institute for Infection Biology, 10117 Berlin, Germany
4 Department for Paediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
5 Department of Microbiology, New York University School of Medicine, New York, NY 10016

Correspondence to Arturo Zychlinsky: zychlinsky{at}mpiib-berlin.mpg.de

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.

V. Brinkmann and A. Zychlinsky contributed equally to this paper.

Abbreviations used in this paper: AT, 3-amino-1,2,4-triazole; CGD, chronic granulomatous disease; DPI, diphenylene iodonium; GO, glucose oxidase; IL, interleukin; LPS, lipopolysaccharide; MNase, micrococcal nuclease; MOI, multiplicity of infection; NETs, neutrophil extracellular traps; PBMC, peripheral blood mononuclear cells; PS, phosphatidylserine; ROS, reactive oxygen species.


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