Gasdermin D plays a vital role in the generation of neutrophil extracellular traps
| Autor: | Peter Nussbaumer, Jan Eickhoff, Gabriel Sollberger, Axel Choidas, Arturo Zychlinsky, Renate Krüger, Garth L. Burn, Peter Habenberger, Sascha Menninger, Raffaella Di Lucrezia, Bert Klebl, Alf Herzig, Susanne Kordes |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteases Programmed cell death Neutrophils Necroptosis Immunology Extracellular Traps Proinflammatory cytokine 03 medical and health sciences Extracellular Animals Humans Cell Death Chemistry Intracellular Signaling Peptides and Proteins Pyroptosis General Medicine Neutrophil extracellular traps Phosphate-Binding Proteins Mice Mutant Strains Neoplasm Proteins Cell biology HEK293 Cells 030104 developmental biology Apoptosis Apoptosis Regulatory Proteins Peptide Hydrolases |
| Zdroj: | Science Immunology. 3 |
| ISSN: | 2470-9468 |
| Popis: | The death of a cell is an inevitable part of its biology. During homeostasis, most cells die through apoptosis. If homeostasis is disturbed, cell death can switch to proinflammatory forms of death, such as necroptosis, pyroptosis, or NETosis. We demonstrate that the formation of neutrophil extracellular traps (NETs), a special form of neutrophil cell death that releases chromatin structures to the extracellular space, is dependent on gasdermin D (GSDMD). GSDMD is a pore-forming protein and an executor of pyroptosis. We screened a chemical library and found a small molecule based on the pyrazolo-oxazepine scaffold that efficiently blocks NET formation and GSDMD-mediated pyroptotic cell death in human cells. During NETosis, GSDMD is proteolytically activated by neutrophil proteases and, in turn, affects protease activation and nuclear expansion in a feed-forward loop. In addition to the central role of GSDMD in pyroptosis, we propose that GSDMD also plays an essential function in NETosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|