Neutrophil extracellular trap cell death requires both autophagy and superoxide generation
| Autor: | Riet De Rycke, Ellen Wirawan, Quinten Remijsen, Eef Parthoens, Jean Willems, Samuel Noppen, Michel Delforge, Peter Vandenabeele, Tom Vanden Berghe, Bob Asselbergh |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Programmed cell death
Neutrophils Apoptosis Granulocyte Granulomatous Disease Chronic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Superoxides Autophagy Extracellular medicine Humans NADH NADPH Oxidoreductases Molecular Biology 030304 developmental biology 0303 health sciences Membrane Glycoproteins NADPH oxidase biology Superoxide NADPH Oxidases Cell Biology Neutrophil extracellular traps Chromatin Assembly and Disassembly 3. Good health Cell biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis NADPH Oxidase 2 biology.protein Tetradecanoylphorbol Acetate Original Article Intracellular |
| Zdroj: | Cell Research; Vol 21 |
| ISSN: | 1748-7838 1001-0602 |
| DOI: | 10.1038/cr.2010.150 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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