T granules in human platelets function in TLR9 organization and signaling

Thon, Jonathan N.; Peters, Christopher G.; Machlus, Kellie R.; Aslam, Rukhsana; Rowley, Jesse W.; MacLeod, Hannah J.; Devine, Matthew T.; Fuchs, Tobias A.; Weyrich, Andrew S.; Semple, John W.; Flaumenhaft, Robert; Italiano, Joseph E.

doi:10.1083/jcb.201111136

Cited by 172 publications

(199 citation statements)

References 42 publications

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“…Recently, a fourth electron-dense tubular system compartment, called the T-granule, was discovered and, intriguingly, colocalizes with TLR9. 27 Many of these proteins translocate to the platelet surface and are released upon platelet activation. Other secreted proteins are located basally on the platelet membrane and/or within other subcellular stores (Table 1).…”

Section: Platelets In Sepsismentioning

confidence: 99%

“…22,27 TLR9 is expressed on the plasma membrane and in the cytoplasm of quiescent human platelets, and its surface expression increases upon activation of platelets with agonists such as thrombin. 27,28 TLR9 is a ligand for unmethylated CpG islands in viral and bacterial DNA, suggesting a previously unrecognized system of pathogen sensing by human platelets. Moreover, TLR9 binds a carboxyalkylpyrrole protein adduct that may serve as a PAMP, resulting in platelet activation, aggregation, and granule secretion and thrombosis.…”

Section: Platelets In Sepsismentioning

confidence: 99%

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Platelets in infectious disease

Middleton

Rondina

2016

Hematology

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Sepsis is a dynamic, acute, infectious disease syndrome characterized by dysregulated thrombo-inflammatory responses. The high mortality associated with sepsis has been recognized since the earliest clinicians' writings. Despite this, advances in the treatment of sepsis have been more modest. This is limited, in part, by the heterogeneity in the definition, population, presentation, and causal factors of infectious syndromes. Given the persistently high morbidity and mortality associated with sepsis, a better understanding of the dysregulated cellular biology underpinning sepsis is needed. Platelets are small, anucleate cells that have hemostatic, inflammatory, and immune-mediating properties. Platelets are the second most common circulating blood cell, and emerging evidence suggests that platelets serve as sentinel and effector cells during infectious syndromes. Nevertheless, the molecular and functional changes that occur in platelets during sepsis, and their impact on the clinical course of infected patients, remain incompletely understood. In this review, we first highlight the complex and dynamic pathophysiology characteristics of acute, systemic infections and we then discuss established and emerging evidence of the roles of platelets in sepsis. Learning Objectives• Understand the systemic pathophysiology and thromboinflammation characteristic of human infectious disease syndromes • Review the role of platelets in sepsis as modulating host hemostatic, inflammatory, and immune activities

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Section: Platelets In Sepsismentioning

confidence: 99%

Section: Platelets In Sepsismentioning

confidence: 99%

Platelets in infectious disease

Middleton

Rondina

2016

Hematology

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“…Тромбоциты, экспрес-сирующие TLR7, вовлечены в ответ организма на вирусные инфекции. TLR9 представлен в тубуляр-ной системе тромбоцитов и действует как рецеп-тор для островков неметилированных последова-тельностей CpG, характерных для бактериальной и вирусной ДНК [14]. Активация тромбоцитов че-рез все перечисленные TLR приводит к высвобож-дению иммуномодулирующих агентов, активации других клеток и представлению им патогенов для фагоцитоза [15].…”

Section: тромбоциты как сенсоры бактерийunclassified

Роль Тромбоцитов В Патогенезе Бактериальных Инфекций

Серебряная¹,

Якуцени²,

Климко³

2017

test

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Резюме Abstract In recent years, a critical mass of information has accumulated, which has made it possible to equate platelets to the cells of innate immunity, which ensures the initiation of inflammation and the reactions of innate immunity. In the presented review platelets were examined from the point of view of antibacterial immune reactions. Mechanisms that allow platelets to recognize bacteria and their soluble products as characteristic of immune cells (via TLR2, TLR4, TLR7 and TLR9, FcγRIIa and receptors for complement components), as well as the mechanisms involved in the hemostasis process (GPIb, GPIIb-IIIa)

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“…ПДИ изобилует в эндоплазматическом ретикулуме ядросодержащих клеток. Она также находится в мелких секреторных гранулах эндотелиальных клеток и т-гранулах тром-боцитов [5,22], а также и во внеклеточном простран-…”

Section: протеин дисульфид изомеразаunclassified

Thiol Isomerases – A Possible Target for Thrombosis Control

Gribkova¹,

Davydovskaya

2017

Racionalʹnaâ farmakoterapiâ v kardiologii

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1 Центр клинических исследований и оценки медицинских технологий, Департамент здравоохранения г. Москвы. Россия, 121096, Москва, ул. Минская, 12 корп. 2 2 Российский национальный исследовательский медицинский университет имени Н.И. Пирогова Россия, 117997, Москва, ул. Островитянова, 1Несмотря на то, что растет количество антитромботических агентов с подтвержденной клинической эффективностью, тромбозы остаются ве-дущей причиной смертности в развитых странах. Поэтому существует необходимость в разработке новых видов терапии с использованием альтернативных мишеней компонентов свертывания крови на основе новых знаний о механизмах тромбообразования. Благодаря новым ме-тодам и подходам к исследованию этих механизмов в последнее время неожиданно было открыто, что в процессы тромбообразования во-влечены внеклеточные тиоловые изомеразы. Протеин дисульфид изомераза (ПДИ) выделяется из тромбоцитов и эндотелиальных клеток после активации и локализуется на поверхности мембраны. Учитывая роль ПДИ в регулировании как агрегации тромбоцитов, так и генерации фиб-рина in vivo, обсуждается возможность использования ПДИ в качестве антитромботической мишени. Тогда как большинство существующих антитромботических средств направлены либо против агрегации тромбоцитов, либо против активации плазменного свертывания, ингиби-торы ПДИ имеют потенциал для предупреждения тромбозов в условиях патологической активации обоих путей, вовлеченных в сложные тром-ботические заболевания, такие как инфаркт миокарда и тромбозы, связанные с онкологическими заболеваниями. В обзоре рассмотрены по-следние данные о роли ПДИ в формировании тромба, основные мишени и механизмы действия, а также ингибиторы ПДИ как кандидаты на новый класс антитромботической терапии с антиагрегантной и антикоагулянтной активностью для предотвращения тромбообразования в организме человека. While there are an increasing number of antithrombotic agents with demonstrated clinical efficacy, thrombosis remains the leading cause of mortality in developed countries. Therefore, there is a need further development of therapies targeting alternative components of the blood clotting mechanism, based on new knowledge about the mechanisms of thrombus formation. Recently, among several unexpected findings of new methods and approaches to the study of these mechanisms it was discovered that protein disulfide isomerase (PDI) serves an essential role in the processes of thrombus formation. PDI is secreted by platelets and endothelial cells following activation and localizes to the membrane surface. Given the role of PDI in regulating both platelet aggregation and fibrin generation in vivo, the possibility of using PDI as an antithrombotic target is discussed. While most antithrombotic target either platelet or coagulation activation, PDI inhibitors have the potential to prevent thrombosis in conditions with pathologic activation of both pathways as implicated in complex thrombotic disorders such as myocardial infarction and cancer associated thrombosis. This review considers what is known about the ...

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T granules in human platelets function in TLR9 organization and signaling

Abstract: TLR9 localizes to a novel intracellular compartment called the T granule to promote immune signaling by platelets.

Cited by 172 publications

References 42 publications

Platelets in infectious disease

Platelets in infectious disease

Роль Тромбоцитов В Патогенезе Бактериальных Инфекций

Thiol Isomerases – A Possible Target for Thrombosis Control

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