The Role of Leukocyte Extracellular Traps in Inflammation and Autoimmunity

Editorial

01 November 2022

Editorial: The role of leukocyte extracellular traps in Inflammation and autoimmunity

Daniel Appelgren

and

Kim Maree O’Sullivan

1,259 views

1 citations

Editors

Impact

Review

29 July 2022

The role of neutrophil extracellular traps in acute lung injury

Davide Scozzi

, 3 more and

Andrew E. Gelman

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability of digesting NET DNA scaffold. Moreover, recent advances in neutrophil biology led to the development of selective NET inhibitors, which also appear to reduce ALI in experimental models. Here we provide an overview of the role of NETs in different forms of ALI discussing existing gaps in our knowledge and novel therapeutic approaches to modulate their impact on lung injury.

12,831 views

72 citations

Plasma smeared poly-l-lysine slides were prepared and stained with MPO antibody (green, AF488), CitH3 (red, AF594) and DAPI (blue) and single channel images were obtained for (A) unstimulated healthy control and (B) PMA stimulated samples. NETs were identified and brightfield images overlapped with specific antibody markers in (B) PMA stimulated sample, therefore confirming the presence of circulating NETs. Individual merged images represent separate donors (n=2). All images were taken on ZEISS Confocal M880 at 20x objective. Set scale 100µm.

Methods

26 July 2022

Detection of neutrophil extracellular traps in patient plasma: method development and validation in systemic lupus erythematosus and healthy donors that carry IRF5 genetic risk

Bharati Matta

, 1 more and

Betsy J. Barnes

10,701 views

12 citations

Original Research

07 July 2022

In Vivo ETosis of Human Eosinophils: The Ultrastructural Signature Captured by TEM in Eosinophilic Diseases

Vitor H. Neves

, 4 more and

Rossana C. N. Melo

5,064 views

22 citations

e., beta cell) and exocrine (acinar) function in T1D. Staging, as defined in (74), with modifications and incorporating assumptions based on available clinical and preclinical data. An arbitrary threshold is set at 25% to indicate functional pancreatic insufficiency. NETosis, neutrophils releasing extracellular traps; PNAs, platelet-neutrophil aggregates.

Mini Review

06 July 2022

The Contribution of Neutrophils and NETs to the Development of Type 1 Diabetes

Alessandra Petrelli

, 4 more and

Charmaine J. Simeonovic

5,596 views

18 citations

Upon stimulation with a wide range of stimuli, innate immune cells release chromatin fibers coated with proteins in a cell death program called suicidal ETosis. Neutrophils can also proceed to ETs extrusion surviving as anucleated cytoplasts that can still exert immune effector functions (vital ETosis). Innate immune cells can even secrete ETs of mtDNA coated with cytoplasmic or granular proteins (Mito-ETs). Mast cells have been reported to release mtDNA concomitantly with degranulation. Microglial cells release ETs, but it is not clear whether this process is associated with cell death. Specific references to different ETs stimuli and types are given in the body of the text. BB1 = basogranulin; β-HE = β-hexosaminidase; Eot. = eotaxin; MMCP-8 = mouse mast cell protease 8. Created with BioRender.com.

Review

01 July 2022

Unveiling Leukocyte Extracellular Traps in Inflammatory Responses of the Central Nervous System

Francesca Colciaghi

and

Massimo Costanza

3,420 views

3 citations

In B cells, CpG-C activation initiates the ejection of full-sized mtDNA that is free of histones (133). Free mtDNA enters the extracellular space in a web-like configuration, independent of TLR-9 activation. Following mtDNA ejection, the cell membrane is preserved, and the number of mitochondria remain unaffected. The cycle is repeated upon CpG-C re-stimulation and mtDNA release is an active process. Whether bacterial ligands can also induce ETs composed of mtDNA in T cells warrants further investigation. mtDNA, mitochondrial DNA; TLR, Toll-like receptor; ATP, Adenosine triphosphate; CpG-C, Synthetic short single-stranded DNA molecules made of cytosine triphosphate deoxynucleotide. Created with BioRender.com.

Review

20 June 2022

T Cell Extracellular Traps: Tipping the Balance Between Skin Health and Disease

Kelsey Ouyang

, 2 more and

George W. Agak

4,945 views

8 citations

Mini Review

12 April 2022

Periodontitis-Derived Dark-NETs in Severe Covid-19

Ljubomir Vitkov

, 6 more and

Martin Herrmann

6,755 views

7 citations

Original Research

12 January 2022

Increased Circulating Cell-Free DNA in Eosinophilic Granulomatosis With Polyangiitis: Implications for Eosinophil Extracellular Traps and Immunothrombosis

Teppei Hashimoto

, 13 more and

Kiyoshi Matsui

Background: Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.

Methods: We enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction before and after the initiation of immunosuppressive therapy. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure of eosinophil extracellular traps (EETs) and neutrophil extracellular traps (NETs) and stability against DNase were assessed in vitro. Platelet adhesion of EETs were also assessed.

Results: Serum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. The structure of EETs showed bolder net-like chromatin threads in vitro and EETs showed greater stability against DNase than NETs. EETs provided a scaffold for platelet adhesion.

Conclusion: cfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs in small-vessel thrombi might contribute to higher concentration of cfDNA and the occurrence of immunothrombosis in EGPA.

9,416 views

44 citations

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