Circulating mitochondrial DAMPs cause inflammatory responses to injury
Qin Zhang,Mustafa Raoof,Yu Chen,Yuka Sumi,Tolga Sursal,Wolfgang G. Junger,Karim Brohi,Kiyoshi Itagaki,Carl J. Hauser +8 more
TLDR
It is shown that injury releases mitochondrial DAMPs into the circulation with functionally important immune consequences, including formyl peptides and mitochondrial DNA, which promote PMN Ca2+ flux and phosphorylation of mitogen-activated protein (MAP) kinases, thus leading to PMN migration and degranulation in vitro and in vivo.Abstract:
Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs) that activate innate immunity. Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs. Here we show that injury releases mitochondrial DAMPs (MTDs) into the circulation with functionally important immune consequences. MTDs include formyl peptides and mitochondrial DNA. These activate human polymorphonuclear neutrophils (PMNs) through formyl peptide receptor-1 and Toll-like receptor (TLR) 9, respectively. MTDs promote PMN Ca(2+) flux and phosphorylation of mitogen-activated protein (MAP) kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTDs can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These signal through innate immune pathways identical to those activated in sepsis to create a sepsis-like state. The release of such mitochondrial 'enemies within' by cellular injury is a key link between trauma, inflammation and SIRS.read more
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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.
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IL-6 in Inflammation, Immunity, and Disease
TL;DR: The mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
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Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
TL;DR: The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging.
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