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Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

(2011) CELL RESEARCH. 21(2). p.290-304
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Neutrophil extracellular traps (NETs) are extracellular chromatin structures that can trap and degrade microbes. They arise from neutrophils that have activated a cell death program called NET cell death, or NETosis. Activation of NETosis has been shown to involve NADPH oxidase activity, disintegration of the nuclear envelope and most granule membranes, decondensation of nuclear chromatin and formation of NETs. We report that in phorbol myristate acetate (PMA)-stimulated neutrophils, intracellular chromatin decondensation and NET formation follow autophagy and superoxide production, both of which are required to mediate PMA-induced NETosis and occur independently of each other. Neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase activity, still exhibit PMA-induced autophagy. Conversely, PMA-induced NADPH oxidase activity is not affected by pharmacological inhibition of autophagy. Interestingly, inhibition of either autophagy or NADPH oxidase prevents intracellular chromatin decondensation, which is essential for NETosis and NET formation, and results in cell death characterized by hallmarks of apoptosis. These results indicate that apoptosis might function as a backup program for NETosis when autophagy or NADPH oxidase activity is prevented.
Keywords
superoxide, chronic granulomatous disease, granulocyte, neutrophil extracellular trap, autophagy, live cell imaging, NADPH OXIDASE, NET FORMATION, APOPTOSIS, MACROAUTOPHAGY, STREPTOCOCCUS, INVOLVEMENT, INHIBITION, ACTIVATION, MECHANISMS, MATURATION

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Citation

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Chicago
Remijsen, Quinten, Tom Vanden Berghe, Ellen Wirawan, Bob Asselbergh, Eef Parthoens, Riet De Rycke, Samuel Noppen, Michel Delforge, Jean Willems, and Peter Vandenabeele. 2011. “Neutrophil Extracellular Trap Cell Death Requires Both Autophagy and Superoxide Generation.” Cell Research 21 (2): 290–304.
APA
Remijsen, Q., Vanden Berghe, T., Wirawan, E., Asselbergh, B., Parthoens, E., De Rycke, R., Noppen, S., et al. (2011). Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. CELL RESEARCH, 21(2), 290–304.
Vancouver
1.
Remijsen Q, Vanden Berghe T, Wirawan E, Asselbergh B, Parthoens E, De Rycke R, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. CELL RESEARCH. 2011;21(2):290–304.
MLA
Remijsen, Quinten, Tom Vanden Berghe, Ellen Wirawan, et al. “Neutrophil Extracellular Trap Cell Death Requires Both Autophagy and Superoxide Generation.” CELL RESEARCH 21.2 (2011): 290–304. Print.
@article{1187330,
  abstract     = {Neutrophil extracellular traps (NETs) are extracellular chromatin structures that can trap and degrade microbes. They arise from neutrophils that have activated a cell death program called NET cell death, or NETosis. Activation of NETosis has been shown to involve NADPH oxidase activity, disintegration of the nuclear envelope and most granule membranes, decondensation of nuclear chromatin and formation of NETs. We report that in phorbol myristate acetate (PMA)-stimulated neutrophils, intracellular chromatin decondensation and NET formation follow autophagy and superoxide production, both of which are required to mediate PMA-induced NETosis and occur independently of each other. Neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase activity, still exhibit PMA-induced autophagy. Conversely, PMA-induced NADPH oxidase activity is not affected by pharmacological inhibition of autophagy. Interestingly, inhibition of either autophagy or NADPH oxidase prevents intracellular chromatin decondensation, which is essential for NETosis and NET formation, and results in cell death characterized by hallmarks of apoptosis. These results indicate that apoptosis might function as a backup program for NETosis when autophagy or NADPH oxidase activity is prevented.},
  author       = {Remijsen, Quinten and Vanden Berghe, Tom and Wirawan, Ellen and Asselbergh, Bob and Parthoens, Eef and De Rycke, Riet and Noppen, Samuel and Delforge, Michel and Willems, Jean and Vandenabeele, Peter},
  issn         = {1001-0602},
  journal      = {CELL RESEARCH},
  language     = {eng},
  number       = {2},
  pages        = {290--304},
  title        = {Neutrophil extracellular trap cell death requires both autophagy and superoxide generation},
  url          = {http://dx.doi.org/10.1038/cr.2010.150},
  volume       = {21},
  year         = {2011},
}

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