Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps
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It is shown that, following priming with granulocyte/macrophage colony-stimulating factor and subsequent short-term toll-like receptor 4 or complement factor 5a receptor stimulation, viable neutrophils are able to generate NETs.Abstract:
Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.read more
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Journal ArticleDOI
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Lorenzo Galluzzi,Lorenzo Galluzzi,Ilio Vitale,Stuart A. Aaronson,John M. Abrams,Dieter Adam,Patrizia Agostinis,Emad S. Alnemri,Lucia Altucci,Ivano Amelio,David W. Andrews,David W. Andrews,Margherita Annicchiarico-Petruzzelli,Alexey V. Antonov,Eli Arama,Eric H. Baehrecke,Nickolai A. Barlev,Nicolas G. Bazan,Francesca Bernassola,Mathieu J.M. Bertrand,Katiuscia Bianchi,Mikhail V. Blagosklonny,Klas Blomgren,Christoph Borner,Patricia Boya,Catherine Brenner,Catherine Brenner,Michelangelo Campanella,Eleonora Candi,Didac Carmona-Gutierrez,Francesco Cecconi,Francis Ka-Ming Chan,Navdeep S. Chandel,Emily H. Cheng,Jerry E. Chipuk,John A. Cidlowski,Aaron Ciechanover,Gerald M. Cohen,Marcus Conrad,Juan R. Cubillos-Ruiz,Peter E. Czabotar,Peter E. Czabotar,Vincenzo D'Angiolella,Ted M. Dawson,Valina L. Dawson,Vincenzo De Laurenzi,Ruggero De Maria,Klaus-Michael Debatin,Ralph J. DeBerardinis,Mohanish Deshmukh,Nicola Di Daniele,Francesco Di Virgilio,Vishva M. Dixit,Scott J. Dixon,Colin S. Duckett,Brian David Dynlacht,Wafik S. El-Deiry,John W. Elrod,Gian Maria Fimia,Simone Fulda,Simone Fulda,Ana J. García-Sáez,Abhishek D. Garg,Carmen Garrido,Carmen Garrido,Evripidis Gavathiotis,Pierre Golstein,Eyal Gottlieb,Eyal Gottlieb,Douglas R. Green,Lloyd A. Greene,Hinrich Gronemeyer,Atan Gross,György Hajnóczky,J. Marie Hardwick,Isaac S. Harris,Michael O. Hengartner,Claudio Hetz,Hidenori Ichijo,Marja Jäättelä,Bertrand Joseph,Philipp J. Jost,Philippe Juin,William J. Kaiser,Michael Karin,Thomas Kaufmann,Oliver Kepp,Adi Kimchi,Richard N. Kitsis,Daniel J. Klionsky,Richard A. Knight,Sharad Kumar,Sam W. Lee,John J. Lemasters,Beth Levine,Andreas Linkermann,Stuart A. Lipton,Richard A. Lockshin,Richard A. Lockshin,Carlos López-Otín,Scott W. Lowe,Scott W. Lowe,Tom Luedde,Enrico Lugli,Marion MacFarlane,Frank Madeo,Michal Malewicz,Walter Malorni,Gwenola Manic,Jean-Christophe Marine,Seamus J. Martin,Jean-Claude Martinou,Jan Paul Medema,Patrick Mehlen,Pascal Meier,Sonia Melino,Edward A. Miao,Jeffery D. Molkentin,Ute M. Moll,Cristina Muñoz-Pinedo,Shigekazu Nagata,Gabriel Núñez,Andrew Oberst,Moshe Oren,Michael Overholtzer,Michele Pagano,Theocharis Panaretakis,Theocharis Panaretakis,Manolis Pasparakis,Josef M. Penninger,David M. Pereira,Shazib Pervaiz,Marcus E. Peter,Mauro Piacentini,Paolo Pinton,Jochen H. M. Prehn,Hamsa Puthalakath,Gabriel A. Rabinovich,Markus Rehm,Rosario Rizzuto,Cecília M. P. Rodrigues,David C. Rubinsztein,Thomas Rudel,Kevin M. Ryan,Emre Sayan,Luca Scorrano,Feng Shao,Yufang Shi,Yufang Shi,John Silke,John Silke,Hans-Uwe Simon,Antonella Sistigu,Brent R. Stockwell,Andreas Strasser,Gyorgy Szabadkai,Gyorgy Szabadkai,Gyorgy Szabadkai,Stephen W.G. Tait,Daolin Tang,Daolin Tang,Nektarios Tavernarakis,Andrew Thorburn,Yoshihide Tsujimoto,Boris Turk,Tom Vanden Berghe,Peter Vandenabeele,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Andreas Villunger,Herbert W. Virgin,Karen H. Vousden,Domagoj Vucic,Erwin F. Wagner,Henning Walczak,David Wallach,Ying Wang,James A. Wells,Will Wood,Junying Yuan,Zahra Zakeri,Boris Zhivotovsky,Boris Zhivotovsky,Laurence Zitvogel,Gerry Melino,Gerry Melino,Guido Kroemer +186 more
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Journal ArticleDOI
Neutrophils in the activation and regulation of innate and adaptive immunity
TL;DR: Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens, but more recent evidence has extended the functions of these cells.
Journal ArticleDOI
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
Lorenzo Galluzzi,Ilio Vitale,Ilio Vitale,Ilio Vitale,John M. Abrams,Emad S. Alnemri,Eric H. Baehrecke,Mikhail V. Blagosklonny,Ted M. Dawson,Valina L. Dawson,Wafik S. El-Deiry,Simone Fulda,Eyal Gottlieb,Douglas R. Green,Michael O. Hengartner,Oliver Kepp,Oliver Kepp,Oliver Kepp,Richard A. Knight,Sharad Kumar,Sharad Kumar,Stuart A. Lipton,Xin Lu,Frank Madeo,Walter Malorni,Patrick Mehlen,Gabriel Núñez,Marcus E. Peter,Mauro Piacentini,David C. Rubinsztein,Yufang Shi,Hans-Uwe Simon,Peter Vandenabeele,Eileen White,Junying Yuan,Boris Zhivotovsky,Gerry Melino,Gerry Melino,Guido Kroemer +38 more
TL;DR: A functional classification of cell death subroutines is proposed that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic programmed cell death, regulated necrosis, autophagic cell death and mitotic catastrophe.
Journal ArticleDOI
Extracellular DNA traps promote thrombosis
Tobias A. Fuchs,Alexander Brill,Daniel Duerschmied,Daphne Schatzberg,Marc Monestier,Daniel D. Myers,Shirley K. Wrobleski,Thomas W. Wakefield,John H. Hartwig,Denisa D. Wagner +9 more
TL;DR: It is reported that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation and may further explain the epidemiological association of infection with thrombosis.
Journal ArticleDOI
Neutrophils, from marrow to microbes.
TL;DR: Neutrophils are produced in the bone marrow from stem cells that proliferate and differentiate to mature neutrophils fully equipped with an armory of granules that contain proteins that enable the neutrophil to deliver lethal hits against microorganisms, but also to cause great tissue damage.
References
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Journal ArticleDOI
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