Journal ArticleDOI
Thrombosis as an intravascular effector of innate immunity
Bernd Engelmann,Steffen Massberg +1 more
TLDR
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.Abstract:
Thrombosis is the most frequent cause of mortality worldwide and is closely linked to haemostasis, which is the biological mechanism that stops bleeding after the injury of blood vessels. Indeed, both processes share the core pathways of blood coagulation and platelet activation. Here, we summarize recent work suggesting that thrombosis under certain circumstances has a major physiological role in immune defence, and we introduce the term immunothrombosis to describe this process. Immunothrombosis designates an innate immune response induced by the formation of thrombi inside blood vessels, in particular in microvessels. Immunothrombosis is supported by immune cells and by specific thrombosis-related molecules and generates an intravascular scaffold that facilitates the recognition, containment and destruction of pathogens, thereby protecting host integrity without inducing major collateral damage to the host. However, if uncontrolled, immunothrombosis is a major biological process fostering the pathologies associated with thrombosis.read more
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Journal ArticleDOI
Extrapulmonary manifestations of COVID-19.
Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Kartik Sehgal,Kartik Sehgal,Nandini Nair,Shiwani Mahajan,Tejasav S. Sehrawat,Behnood Bikdeli,Behnood Bikdeli,Neha Ahluwalia,John C. Ausiello,Elaine Wan,Daniel E. Freedberg,Ajay J. Kirtane,Sahil A. Parikh,Mathew S. Maurer,Anna S. Nordvig,Domenico Accili,Joan M. Bathon,Sumit Mohan,Kenneth A. Bauer,Kenneth A. Bauer,Martin B. Leon,Harlan M. Krumholz,Nir Uriel,Mandeep R. Mehra,Mitchell S.V. Elkind,Mitchell S.V. Elkind,Gregg W. Stone,Allan Schwartz,David D. Ho,John P. Bilezikian,Donald W. Landry +33 more
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Journal ArticleDOI
COVID-19 and its implications for thrombosis and anticoagulation.
Jean M. Connors,Jerrold H. Levy +1 more
TL;DR: COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagULopathy or DIC.
Journal ArticleDOI
The immunopathology of sepsis and potential therapeutic targets
TL;DR: Pivotal for the clinical development of new sepsis therapies is the selection of patients on the basis of biomarkers and/or functional defects that provide specific insights into the expression or activity of the therapeutic target.
Journal ArticleDOI
Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome.
Elizabeth A. Middleton,Xue-Yan He,Frederik Denorme,Robert A. Campbell,David Ng,Steven P. Salvatore,Steven P. Salvatore,Maria Mostyka,Amelia Baxter-Stoltzfus,Alain C. Borczuk,Alain C. Borczuk,Massimo Loda,Massimo Loda,Mark J. Cody,Bhanu Kanth Manne,Irina Portier,Estelle S. Harris,Aaron C. Petrey,Ellen J. Beswick,Aleah F. Caulin,Anthony J. Iovino,Lisa M. Abegglen,Andrew S. Weyrich,Matthew T. Rondina,Mikala Egeblad,Joshua D. Schiffman,Christian C. Yost +26 more
TL;DR: NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.
Journal ArticleDOI
NETosis: how vital is it?
Bryan G. Yipp,Paul Kubes +1 more
TL;DR: The evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity is examined and how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release is examined.
References
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Journal ArticleDOI
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
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Journal ArticleDOI
Getting to the site of inflammation: the leukocyte adhesion cascade updated
TL;DR: This Review focuses on new aspects of one of the central paradigms of inflammation and immunity — the leukocyte adhesion cascade.
Journal ArticleDOI
LPS induction of gene expression in human monocytes
Mausumee Guha,Nigel Mackman +1 more
TL;DR: This work has elucidated how LPS is recognized by monocytes and macrophages of the innate immune system and activates a variety of transcription factors that include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate the induction of many genes encoding inflammatory mediators.
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
TL;DR: It is proposed that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis, where NETs have the greatest capacity for bacterial trapping.
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