The coming of age of neutrophil extracellular traps in thrombosis: Where are we now and where are we headed?

Bruggen, Stijn Van; Martinod, Kimberly

doi:10.1111/imr.13179

Cited by 19 publications

(24 citation statements)

References 265 publications

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“…NETs are extracellular structures composed of granule, nuclear, and mitochondrial constituents assembled on a scaffold of decondensed chromatin with antimicrobial proteins and peptides [ 26 , 27 ]. NETs act as a scaffold for platelets, red blood cells, extracellular vesicles, VWF, and TF [ 28 ].…”

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

“…NETs act as a scaffold for platelets, red blood cells, extracellular vesicles, VWF, and TF [ 28 ]. NETs play a crucial role in host defense and pathogen clearance during infection [ 29 ]; however, dysregulation of NETs can lead to autoimmune, inflammatory, and pathological thrombotic disorders [ 26 , 27 , 28 ]. Histone proteins, that are one of the constituents of NETs (in addition to DNA), are potent DAMP molecules also capable of initiating a positive inflammatory feedback loop [ 26 ].…”

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

“…Within thrombi formed in vivo, NETs colocalize with VWF [ 30 ]. Finally, NET fibers contain various other factors that can render them procoagulant, such as serine proteases that inhibit TFPI, and in addition, TF has been shown to be deposited on NETs [ 26 , 28 ].…”

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

“…Following virus recognition, specific TLRs activate PAD 4 directly [ 35 ]. When this process occurs without control, thrombus formation appears and, if chronified, it can lead to tissue damage resulting in fibrosis, organ dysfunction, and death [ 26 ].…”

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

“…In fact, heparin, one of the most common anticoagulants, at high concentrations, is able to degrade NETs and also neutralize histones in blood. Furthermore, antiplatelet drugs, such as aspirin or ticagrelor, inhibit NET release [ 26 ].…”

Section: Immunothrombosis As a New Therapeutical Targetmentioning

confidence: 99%

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Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives

Marcos-Jubilar

Paramo

2023

JCM

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Thromboinflammation or immunothrombosis is a concept that explains the existing link between coagulation and inflammatory response present in many situations, such as sepsis, venous thromboembolism, or COVID-19 associated coagulopathy. The purpose of this review is to provide an overview of the current data regarding the mechanisms involved in immunothrombosis in order to understand the new therapeutic strategies focused in reducing thrombotic risk by controlling the inflammation.

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Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

Section: Role Of Nets In Immunothrombosismentioning

confidence: 99%

Section: Immunothrombosis As a New Therapeutical Targetmentioning

confidence: 99%

See 3 more Smart Citations

Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives

Marcos-Jubilar

Paramo

2023

JCM

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The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis

Song,

Zhang,

Bai

et al. 2023

Advanced Science

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Tissue‐infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro‐inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain‐containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil‐intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63‐linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER‐to‐Golgi trafficking, thus restricting the surface expression of integrin‐regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1‐deficient TINs and attenuates inflammation‐induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation.

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Inflammation‐, immunothrombosis,‐ and autoimmune‐feedback loops may lead to persistent neutrophil self‐stimulation in long COVID

Thierry,

Salmon

2024

Journal of Medical Virology

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Understanding the pathophysiology of long COVID is one of the most intriguing challenges confronting contemporary medicine. Despite observations recently made in the relevant molecular, cellular, and physiological domains, it is still difficult to say whether the post‐acute sequelae of COVID‐19 directly correspond to the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This work hypothesizes that neutrophils and neutrophil extracellular traps (NETs) production are at the interconnection of three positive feedback loops which are initiated in the acute phase of SARS‐CoV‐2 infection, and which involve inflammation, immunothrombosis, and autoimmunity. This phenomenon could be favored by the fact that SARS‐CoV‐2 may directly bind and penetrate neutrophils. The ensuing strong neutrophil stimulation leads to a progressive amplification of an exacerbated and uncontrolled NETs production, potentially persisting for months beyond the acute phase of infection. This continuous self‐stimulation of neutrophils leads, in turn, to systemic inflammation, micro‐thromboses, and the production of autoantibodies, whose significant consequences include the persistence of endothelial and multiorgan damage, and vascular complications.

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The coming of age of neutrophil extracellular traps in thrombosis: Where are we now and where are we headed?

Cited by 19 publications

References 265 publications

Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives

Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives

The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis

Inflammation‐, immunothrombosis,‐ and autoimmune‐feedback loops may lead to persistent neutrophil self‐stimulation in long COVID

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