Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis

Paryzhak, Solomiya; Dumych, Tetiana; Mahorivska, I; Boichuk, M.O.; Bila, Galyna; Peshkova, Svetlana; Nehrych, Tetyana; Bilyy, Rostyslav

doi:10.1080/08916934.2018.1514390

Cited by 23 publications

(19 citation statements)

References 34 publications

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“…The higher content of fibrin fibers in the head and tail may impede the platelet contractile forces, reducing formation of polyhedrocytes. This may impair contractility, making this region more prone to embolization, because impaired clot contraction has been shown to correlate with a higher incidence of pulmonary embolism in patients with deep venous thromboembolism 43 .…”

Section: Discussionmentioning

confidence: 99%

The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli

Chernysh

Nagaswami

Kosolapova

et al. 2020

Sci Rep

167

174

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Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo. polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. the structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro. There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders. Thromboembolism remains a leading cause of death and disability. Thrombi may partially or totally obstruct arteries or veins, leading to local ischemic complications and they can embolize to the cerebral arteries and lungs, where they may cause stroke or other life-threatening conditions. There are approximately 1 million incident cases of deep venous thromboembolism each year and over 60,000 deaths per year from recognized pulmonary embolism in the United States alone 1,2. Over 900,000 patients are hospitalized each year for management of acute myocardial infarction, which is responsible for 1 in every 6 deaths in the US, and about 800,000 patients suffer from stroke each year with 87% of all strokes being ischemic. Stroke kills about 140,000 people each year, or 1 in 20 deaths in the US 3. Insights into the pathophysiology of thrombotic disorders have come from studies using a variety of designs, ranging from detailed in vitro molecular and cellular approaches, ex vivo pathological studies, in silico multiscale thrombosis modeling to in vivo animal models and clinical trials. Yet, there are remarkably few detailed analyses of thrombus structure that further our understanding of their relationship to vascular origin and duration in vivo, as well as the composition or the internal structural features of thrombi most closely associated with the risk of embolization. The composition, physical properties, and evolution of venous and arterial thrombi are likely to differ mainly due to various local conditions and time since formation. Platelets play an important role in the development of arterial thrombi formed at relatively high wall shear rates (~10 2-10 5 s −1), generating what are often ...

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Section: Discussionmentioning

confidence: 99%

The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli

Chernysh

Nagaswami

Kosolapova

et al. 2020

Sci Rep

167

174

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“…However, real proof that NETs contribute to BBB breakdown in MS still needs to be provided. Another role attributed to NETs is the cleavage of circulating immune complexes in MS, as proposed by Paryzhak et al [ 135 ]. They highlighted the potential of NET-related proteases to modify circulating IgG immune complexes, leading to the unfolding of internal glycoepitopes.…”

Section: Neutrophil Effector Functions and Their Link To Ms Pathogmentioning

confidence: 99%

Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

Bondt

Hellings

Opdenakker

et al. 2020

IJMS

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Neutrophils are the most abundant circulating and first-responding innate myeloid cells and have so far been underestimated in the context of multiple sclerosis (MS). MS is the most frequent, immune-mediated, inflammatory disease of the central nervous system. MS is treatable but not curable and its cause(s) and pathogenesis remain elusive. The involvement of neutrophils in MS pathogenesis has been suggested by the use of preclinical animal disease models, as well as on the basis of patient sample analysis. In this review, we provide an overview of the possible mechanisms and functions by which neutrophils may contribute to the development and pathology of MS. Neutrophils display a broad variety of effector functions enabling disease pathogenesis, including (1) the release of inflammatory mediators and enzymes, such as interleukin-1β, myeloperoxidase and various proteinases, (2) destruction and phagocytosis of myelin (as debris), (3) release of neutrophil extracellular traps, (4) production of reactive oxygen species, (5) breakdown of the blood–brain barrier and (6) generation and presentation of autoantigens. An important question relates to the issue of whether neutrophils exhibit a predominantly proinflammatory function or are also implicated in the resolution of chronic inflammatory responses in MS.

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“…(B) NETs can be utilized to detect ANCAs on NET-covered microbeads in flurocytometric assays (Roitsch et al [5]). (C) The modification of autoantibodies in MS by NET proteases alters glycan accessibility (Paryzhak et al [8]). (D) NET Formation has vast implications in autoimmune diseases.…”

Section: Net Involvement In Disease Onset Progression and Severitymentioning

confidence: 99%

“…NETs are decorated with active enzymes like neutrophil proteases and can degrade cytokines. Paryzhak et al [8] wondered whether glycosidases are active on NETs. They searched for the occurrence of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in patients suffering from multiple sclerosis.…”

Section: Modifying Autoantibodies With Netsmentioning

confidence: 99%

Editorial – NETs in autoimmune diseases

Boeltz

Herrmann

2018

Autoimmunity

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Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis

Cited by 23 publications

References 34 publications

The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli

The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli

Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

Editorial – NETs in autoimmune diseases

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