Gasdermin D plays a vital role in the generation of neutrophil extracellular traps.

Science Immunology
Gabriel SollbergerArturo Zychlinsky

Abstract

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.

References

Mar 6, 2004·Science·Volker BrinkmannArturo Zychlinsky
Jan 11, 2007·The Journal of Cell Biology·Tobias A FuchsArturo Zychlinsky
Sep 24, 2010·British Journal of Pharmacology·S WindK Wingler
Oct 27, 2010·The Journal of Cell Biology·Venizelos PapayannopoulosArturo Zychlinsky
Nov 10, 2010·Cell Research·Quinten RemijsenPeter Vandenabeele
Dec 21, 2010·Nature Chemical Biology·Abdul HakkimHerbert Waldmann
Oct 18, 2011·Nature·Nobuhiko KayagakiVishva M Dixit
Sep 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariana J Kaplan, Marko Radic
Apr 22, 2014·Cell Reports·Meritxell ReverterCarlos Enrich
Oct 17, 2014·Nature·Yong ShiQiusheng Gu
Aug 4, 2015·Current Protocols in Immunology·Muthulekha SwamydasMichail S Lionakis
Sep 17, 2015·Nature·Nobuhiko KayagakiVishva M Dixit
Dec 20, 2015·Current Opinion in Immunology·H N StephensonA Zychlinsky
Jun 25, 2016·Proceedings of the National Academy of Sciences of the United States of America·Robin A AgliettiErin C Dueber
Jul 16, 2016·The EMBO Journal·Lorenzo SborgiSebastian Hiller
Mar 8, 2017·Nature Medicine·Selina K Jorch, Paul Kubes
Jun 3, 2017·ELife·Elaine F KennyArturo Zychlinsky
Nov 7, 2017·Developmental Cell·Borko AmulicArturo Zychlinsky
Mar 15, 2018·Cell Reports·Hiroto KambaraHongbo R Luo

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Citations

Sep 30, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan SunEric Pearlman
Dec 28, 2018·Biology of Reproduction·Jonathan FaroNardhy Gomez-Lopez
Mar 8, 2019·FEMS Microbiology Reviews·Tomasz Skirecki, Jean-Marc Cavaillon
Mar 22, 2019·Journal of Leukocyte Biology·Marco Túlio R GomesSergio C Oliveira
Feb 21, 2019·Journal of Lipid Research·Alan R Tall, Marit Westerterp
Mar 21, 2019·Allergy·Kazuhiko MaedaShizuo Akira
Apr 16, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Patrick M LelliottCevayir Coban
Mar 23, 2019·Blood·Fernanda V S Castanheira, Paul Kubes
Jul 19, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Charlotte ThålinHåkan Wallén
Aug 17, 2019·Biomolecules·Mithunan RavindranNades Palaniyar
Aug 29, 2019·American Journal of Reproductive Immunology : AJRI·Nardhy Gomez-LopezChaur-Dong Hsu
Sep 27, 2019·Journal of Leukocyte Biology·Arjun SukumaranJennifer Geddes-McAlister
Sep 8, 2019·Science Immunology·Judy LiebermanJonathan C Kagan
Oct 20, 2019·Science Immunology·Sebastian Lorenz KnackstedtBorko Amulic
Nov 7, 2019·Nature Reviews. Immunology·Petr BrozFeng Shao
Aug 28, 2019·Cold Spring Harbor Perspectives in Biology·Shiyu XiaHao Wu
Apr 3, 2020·Journal of Cell Communication and Signaling·Danbin WuMaojuan Guo
Apr 24, 2020·Journal of Leukocyte Biology·Pak-Hin Hinson CheungDong-Yan Jin
Feb 6, 2020·Annual Review of Immunology·Sannula KesavardhanaThirumala-Devi Kanneganti
Feb 1, 2020·Annual Review of Immunology·Xing Liu, Judy Lieberman
Oct 2, 2019·Cold Spring Harbor Perspectives in Biology·Nathalia M de Vasconcelos, Mohamed Lamkanfi
Jun 13, 2020·Journal of Leukocyte Biology·Warrison A Andrade, Dario S Zamboni
Jun 13, 2020·Journal of Leukocyte Biology·Pontus Orning, Egil Lien
Jun 23, 2020·Immunological Reviews·Benjamin DemarcoPetr Broz
Nov 27, 2019·Cold Spring Harbor Perspectives in Biology·Sabrina Sofia Burgener, Kate Schroder
Aug 30, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Manuel ReithoferBeatrice Jahn-Schmid
Sep 6, 2020·Apoptosis : an International Journal on Programmed Cell Death·Chaoyi WuShuyan Wu
Jul 15, 2020·Annual Review of Microbiology·Katherine Andrea SchubertVictoria Auerbuch
Sep 19, 2020·Proceedings of the National Academy of Sciences of the United States of America·Hawa Racine ThiamClare M Waterman
Sep 25, 2019·The Journal of Experimental Medicine·Pontus OrningKatherine A Fitzgerald
Apr 18, 2020·The Journal of Experimental Medicine·Betsy J BarnesMikala Egeblad
Jul 31, 2020·The Journal of Clinical Investigation·Simon J ClearyMark R Looney
Dec 25, 2019·Journal of Immunology Research·Fangyuan YangErwei Sun
Dec 17, 2019·Cell Death Discovery·Chong-Shan Shi, John H Kehrl
Aug 21, 2020·Science·Fiachra HumphriesKatherine A Fitzgerald
Sep 26, 2020·Frontiers in Immunology·Changhoon OhYoussef Aachoui
Oct 6, 2020·Frontiers in Cellular and Infection Microbiology·Gaurav ShrivastavaEric Calvo
May 23, 2019·Frontiers in Immunology·Elvira SondoNicoletta Pedemonte
Jan 23, 2020·Cells·Aldo BonaventuraFabrizio Montecucco

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis