Anti-β2GPI/β2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation

Zha, Caijun; Zhang, Wenjing; Gao, Fei; Xu, Jiangnan; Jia, Ruichun; Cai, Jinquan; Liu, Yanhong

doi:10.1016/j.neuropharm.2018.06.001

Cited by 44 publications

(48 citation statements)

References 69 publications

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“…Примечательным является наличие взаимосвязи повышенного уровня антифосфолипидных аутоантител и сердечно-сосудистых осложнений атеросклероза именно у лиц без диагностированных аутоиммунных патологий [4]. Возможный патогенетический механизм, объясняющий наличие этой связи, недавно был продемонстрирован на примере иммунных комплексов с 2-ГП1, запускающих процесс нетоза с последующей активацией и агрегацией тромбоцитов [33].…”

Section: Discussionunclassified

Сравнительная характеристика сорбентов для удаления иммуноглобулинов (сравнение in vitro)

Afanasieva¹,

Dmitrieva²,

Afanasieva³

et al. 2019

Kardiologicheskii Vestnik

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Цель исследования. Методы терапевтического афереза в мировой клинической практике считаются эффективными для лечения тяже5 лых заболеваний аутоиммунной природы в качестве как первой, так и второй линии терапии. В настоящее время для специфического удаления иммуноглобулинов (Ig) широко используются различные плазмосорбенты с иммобилизованными природными и синтетически5 ми лигандами. Нами был синтезирован новый сорбент, пригодный для гемоперфузии. Предлагаемая работа посвящена исследованию свойств гемосорбента в сравнении с одним из широко используемых плазмосорбентов. Материал и методы. В работе были использованы сорбент с поликлональными антителами к иммуноглобулинам G человека (плазмосорбент) и сорбент с синтетическим лигандом, иммо5 билизованным на макрогранулированную матрицу (гемосорбент). Оценивали динамику концентрации различных классов и подклассов IgG, специфических антифосфолипидных и анти5ДНК5 аутоантител, а также С5реактивного белка (СРБ) в условиях проведения экспе5 риментов in vitro. Результаты. Исследованные сорбенты обладали сравнимой эффективностью удаления IgG и IgА (60 и 32 против 47 и 35 на плазмо5 и гемосорбенте соответственно). Однако IgM связывались только с плазмосорбентом (28). При этом гемосорбент с большей эффективностью связывал подклассы IgG3 и IgG4, а также специфические аутоантитела против двухцепочечной (дц) и денату5 рированной одноцепочечной (оц) ДНК. В отличие от плазмосорбента гемосорбент был способен с высокой эффективностью связывать и удалять из плазмы СРБ. Гемосорбент с иммобилизованным синтетическим лигандом был инертен относительно клеток крови и обладал гемосовместимостью в экспериментах in vitro при перфузии цельной крови. Выводы. Как плазмосорбент, так и гемосорбент, одинаково эффективно удаляют Ig основных классов (IgG и IgA), подклассы IgG и специфические антифосфолипидные и анти5ДНК аутоантитела. Создание сорбента для удаления IgG, подходящего для перфузии цельной крови, позволит расширить применение методов терапевтиче5 ского афереза для лечения пациентов с аутоиммунными и, возможно, сопутствующими сердечно5сосудистыми заболеваниями.Background. Therapeutic apheresis methods are applied in the world clinical practice as one of the effective approaches for treatment of severe autoimmune diseases, both as first5line and second5line therapy. Currently plasmаsorbents with immobilized native and synthetic ligands are widely used for specific removal of immunoglobulins. We have developed and investigated the new hemosorbent and compared it with one of the used plasmasorbents. Methods. In our study weve compared immunosorbent with sheep polyclonal antibodies against human immunoglobulin G and the sorbent with synthetic ligand, immobilized on cross5linked macro beads agarose matrix. Weve tested in vitro at the same conditions the efficiency of removal of Ig classes and subclasses, autoantibodies against DNA and antiphospholipid autoantibodies, and also C5reactive protein. Results. Both sorbents have almost equal efficiency of IgG and IgA removal 60 and 32 for plasmasorbent and 47 and 35 for hemosorbent. But IgM were removed only by plasmasorbent (28). The hemosorbent have binded more effective such subclasses of immunoglobulins as IgG3 and IgG4, and also specific autoantibodies to single or double stranded DNA. Hemosorbent have removed C5reactive protein very effective. Hemocompatibility of hemosorbent was verified by inertness with human blood cells. Conclusions. Ig5plasmasorbent and Ig5hemosorbent have the same efficacy for removal of Ig classes, IgG subclasses, antiphospholipid and others pathogenic autoantibodies. But Ig5hemosorbent is more successful in C5reactive protein binding compared to Ig5plasmasorbent and it is hemocompatible.

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Section: Discussionunclassified

Сравнительная характеристика сорбентов для удаления иммуноглобулинов (сравнение in vitro)

Afanasieva¹,

Dmitrieva²,

Afanasieva³

et al. 2019

Kardiologicheskii Vestnik

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“…Furthermore, neutrophils from APS patients were shown to display enhanced spontaneous NET release [134,142]. NET response might be mediated through activation of TLR4 [100,142], together with reactive oxygen species (ROS) [100,142,143]. Remarkably, IgG purified from APS patients induced NET release from healthy neutrophils [142].…”

Section: Antiphospholipid Syndrome (Aps)mentioning

confidence: 99%

“…An increase in NET release in response to autoantibodies could be explained by the presence of β2-GP1 on the surface of neutrophils [142]. Several studies observed anti-β2-GP1 to induce NET formation in healthy neutrophils [100,142,143]. Evidences suggest that NETs may directly mediate APS pathology by featuring as a scaffold for platelets to aggregate [144], possibly by presenting a tissue factor [53,100].…”

Section: Antiphospholipid Syndrome (Aps)mentioning

confidence: 99%

“…Several studies observed anti-β2-GP1 to induce NET formation in healthy neutrophils [100,142,143]. Evidences suggest that NETs may directly mediate APS pathology by featuring as a scaffold for platelets to aggregate [144], possibly by presenting a tissue factor [53,100]. Moreover, activated platelets can stimulate neutrophils to NET formation by releasing HMGB1 [141].…”

Section: Antiphospholipid Syndrome (Aps)mentioning

confidence: 99%

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Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses

Fousert

Toes

Desai

2020

Cells

167

128

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Following fifteen years of research, neutrophil extracellular traps (NETs) are widely reported in a large range of inflammatory infectious and non-infectious diseases. Cumulating evidences from in vitro, in vivo and clinical diagnostics suggest that NETs may play a crucial role in inflammation and autoimmunity in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Most likely, NETs contribute to breaking self-tolerance in autoimmune diseases in several ways. During this review, we discuss the current knowledge on how NETs could drive autoimmune responses. NETs can break self-tolerance by being a source of autoantigens for autoantibodies found in autoimmune diseases, such as anti-citrullinated protein antibodies (ACPAs) in RA, anti-dsDNA in SLE and anti-myeloperoxidase and anti-protein 3 in AAV. Moreover, NET components could accelerate the inflammatory response by mediating complement activation, acting as danger-associated molecular patterns (DAMPs) and inflammasome activators, for example. NETs also can activate other immune cells, such as B cells, antigen-presenting cells and T cells. Additionally, impaired clearance of NETs in autoimmune diseases prolongs the presence of active NETs and their components and, in this way, accelerate immune responses. NETs have not only been implicated as drivers of inflammation, but also are linked to resolution of inflammation. Therefore, NETs may be central regulators of inflammation and autoimmunity, serve as biomarkers, as well as promising targets for future therapeutics of inflammatory autoimmune diseases.

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“…β2-GPI is a glycoprotein that specifically binds to oxidized products of phospholipids and cholesteryl esters and acts as a major target antigen for antiphospholipid antibodies developed in autoimmune diseases, including antiphospholipid syndrome and SLE [137]. Interestingly, the anti-β2-GPI/β2-GPI immune complex acts on neutrophils to induce NET formation associated with platelet aggregation, leading to enhanced thrombus formation [138]. These data indicate that the oxLDL/β2-GPI complex and/or its immune complex may also contribute to the development of vascular complications in SLE through upregulation of NET formation.…”

Section: Significance Of Oxldl In Autoimmune Diseasesmentioning

confidence: 99%

Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

Obama

Itabe

2020

IJMS

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Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.

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Anti-β2GPI/β2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation

Cited by 44 publications

References 69 publications

Сравнительная характеристика сорбентов для удаления иммуноглобулинов (сравнение in vitro)

Сравнительная характеристика сорбентов для удаления иммуноглобулинов (сравнение in vitro)

Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses

Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

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