Journal ArticleDOI
Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases
Steffen Massberg,Lenka Grahl,Marie-Luise von Bruehl,Davit Manukyan,Susanne Pfeiler,Christian Goosmann,Volker Brinkmann,Michael Lorenz,Kiril Bidzhekov,Avinash Khandagale,Ildiko Konrad,Elisabeth Kennerknecht,Katja Reges,Stefan Holdenrieder,Siegmund Braun,Christoph Reinhardt,Michael Spannagl,Klaus T. Preissner,Bernd Engelmann +18 more
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TLDR
The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense, although the molecular determinants and in vivo significance of this association remain unclear.Abstract:
Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.read more
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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.
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Atherosclerosis: current pathogenesis and therapeutic options
Christian Weber,Heidi Noels +1 more
TL;DR: This work aims to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD.
Journal ArticleDOI
Neutrophil extracellular traps in immunity and disease
TL;DR: The identification of molecules that modulate the release of NETs has helped to refine the view of the role of neutrophils in immune protection, inflammatory and autoimmune diseases and cancer.
Journal ArticleDOI
Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo
Marie-Luise von Brühl,Konstantin Stark,Alexander Steinhart,Sue Chandraratne,Ildiko Konrad,Michael Lorenz,Alexander G. Khandoga,Anca Tirniceriu,Raffaele Coletti,Maria Köllnberger,Robert A. Byrne,Iina Laitinen,Axel Walch,Alexander Brill,Susanne Pfeiler,Davit Manukyan,Siegmund Braun,Philipp S. Lange,Julia Riegger,Jerry Ware,Annekathrin Eckart,Selgai Haidari,Martina Rudelius,Christian Schulz,Katrin Echtler,Volker Brinkmann,Markus Schwaiger,Klaus T. Preissner,Denisa D. Wagner,Nigel Mackman,Bernd Engelmann,Steffen Massberg +31 more
TL;DR: Deep vein thrombosis initiation is mediated by cross talk between monocytes, neutrophils, and platelets.
Journal ArticleDOI
Thrombosis as an intravascular effector of innate immunity
Bernd Engelmann,Steffen Massberg +1 more
TL;DR: Recent work suggesting that thrombosis under certain circumstances has a major physiological role in immune defence is summarized, and the term immunothromBosis is introduced to describe this process.
References
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Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
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Tobias A. Fuchs,Ulrike Abu Abed,Christian Goosmann,Robert Hurwitz,Ilka Schulze,Volker Wahn,Yvette Weinrauch,Volker Brinkmann,Arturo Zychlinsky +8 more
TL;DR: This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.
Journal ArticleDOI
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
Stephen Clark,Adrienne C. Ma,Samantha A. Tavener,Braedon McDonald,Zahra Goodarzi,Margaret M. Kelly,Kamala D. Patel,Subhadeep Chakrabarti,Erin F. McAvoy,Gary D. Sinclair,Elizabeth Keys,Emma Allen-Vercoe,Rebekah DeVinney,Christopher J. Doig,Francis H. Y. Green,Paul Kubes +15 more
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How neutrophils kill microbes
TL;DR: Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase, but this is incorrect.
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Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo
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