Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia

Oyarzún, Cecilia Paola Marin; Glembotsky, Ana Claudia; Goette, Nora Paula; Lev, Paola Roxana; Luca, Geraldine De; Pietto, Maria Constanza Baroni; Moiraghi, Beatriz; Ríos, Miguel A. Castro; Vicente, Ascensión; Marta, Rosana Fernanda; Schattner, Mirta; Heller, Paula G.

doi:10.3389/fimmu.2020.00705

Cited by 37 publications

(35 citation statements)

References 41 publications

(72 reference statements)

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“…Interestingly, no change in cell-surface expression of platelet-TLR2 was observed in septic patients, compared with both healthy and non-infectious controls within the intensive care unit [ 81 ] and this is despite infection inducing a similar magnitude of acute inflammatory response as that seen in ACS. Similarly, compared to healthy controls, no augmentation in platelet-TLR2 expression was seen in patients with essential thrombocythemia, a clinical condition associated with sustained thrombocytosis and thrombo-inflammation [ 82 ]. Platelet-TLR2 seems to be regulated variably during inflammation and seems likely to be important for the inflammatory response to cardiovascular pathology.…”

Section: An Update On Platelet-tlr Expression and Tlr-mediated Plamentioning

confidence: 99%

“…Within the AF cohort, the greater time spent in AF (persistent vs. paroxysmal) was associated with an increase in platelet-TLR4 expression [ 80 ]. In contrast, no modulation of platelet-TLR4 expression is seen in patients with Essential Thrombocythemia, compared to healthy controls [ 82 ]. However, the culmination of these results suggests that platelet-TLR4 is actively upregulated during most clinical forms of infectious and injurious inflammation.…”

Section: An Update On Platelet-tlr Expression and Tlr-mediated Plamentioning

confidence: 99%

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Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Hally

Fauteux‐Daniel

Hamzeh‐Cognasse

et al. 2020

IJMS

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While platelet function has traditionally been described in the context of maintaining vascular integrity, recent evidence suggests that platelets can modulate inflammation in a much more sophisticated and nuanced manner than previously thought. Some aspects of this expanded repertoire of platelet function are mediated via expression of Toll-like receptors (TLRs). TLRs are a family of pattern recognition receptors that recognize pathogen-associated and damage-associated molecular patterns. Activation of these receptors is crucial for orchestrating and sustaining the inflammatory response to both types of danger signals. The TLR family consists of 10 known receptors, and there is at least some evidence that each of these are expressed on or within human platelets. This review presents the literature on TLR-mediated platelet activation for each of these receptors, and the existing understanding of platelet-TLR immune modulation. This review also highlights unresolved methodological issues that potentially contribute to some of the discrepancies within the literature, and we also suggest several recommendations to overcome these issues. Current understanding of TLR-mediated platelet responses in influenza, sepsis, transfusion-related injury and cardiovascular disease are discussed, and key outstanding research questions are highlighted. In summary, we provide a resource—a “researcher’s toolkit”—for undertaking further research in the field of platelet-TLR biology.

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Section: An Update On Platelet-tlr Expression and Tlr-mediated Plamentioning

confidence: 99%

Section: An Update On Platelet-tlr Expression and Tlr-mediated Plamentioning

confidence: 99%

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Hally

Fauteux‐Daniel

Hamzeh‐Cognasse

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In the last decade, there has been increasing evidence that platelets do much more than just maintain hemostasis and thrombosis. Many studies demonstrated their contribution to immunity and a pivotal role in developing inflammation, infections, and cancer [ 26 , 27 , 28 , 29 , 30 , 31 ]. Circulating platelets function as guardians sensing pathogens by a set of pattern recognition receptors (PRRs), including TLR, nod-like receptors (NLR), and C-type lectin receptors (CLR).…”

Section: Platelets Biology and Functionsmentioning

confidence: 99%

Proteomics: A Tool to Study Platelet Function

Shevchuk

Begonja

Gambaryan

et al. 2021

IJMS

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Platelets are components of the blood that are highly reactive, and they quickly respond to multiple physiological and pathophysiological processes. In the last decade, it became clear that platelets are the key components of circulation, linking hemostasis, innate, and acquired immunity. Protein composition, localization, and activity are crucial for platelet function and regulation. The current state of mass spectrometry-based proteomics has tremendous potential to identify and quantify thousands of proteins from a minimal amount of material, unravel multiple post-translational modifications, and monitor platelet activity during drug treatments. This review focuses on the role of proteomics in understanding the molecular basics of the classical and newly emerging functions of platelets. including the recently described role of platelets in immunology and the development of COVID-19.The state-of-the-art proteomic technologies and their application in studying platelet biogenesis, signaling, and storage are described, and the potential of newly appeared trapped ion mobility spectrometry (TIMS) is highlighted. Additionally, implementing proteomic methods in platelet transfusion medicine, and as a diagnostic and prognostic tool, is discussed.

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“…Gangaraju et al conducted unbiased RNA sequencing and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes in granulocytes and platelets of PV patients, especially in patients with a history of thrombosis [116]. Marín Oyarzún et al recently highlighted an additional inflammation/hypercoagulation cycle by demonstrating that hyperactive toll-like receptor (TLR) responses on platelet are characteristic in patients with ET and promote platelet activation, platelet interaction with leukocytes and the endothelium and secretion of inflammatory mediators [117]. In recent years the concept of 'thrombo-inflammation' was conceptualized to express the intimate cross-talk and mutual perpetuating effects of inflammation and thrombosis one upon the other [118].…”

Section: Thrombo-inflammation and Clonal Hematopoiesismentioning

confidence: 99%

Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?

Wolach

Abulafia

2021

Hemato

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Despite recent advances in diagnosis and therapy, arterial and venous thrombosis remain a major cause of morbidity and mortality in Philadelphia-negative myeloproliferative neoplasms (MPNs). Preventing and treating arterial and venous thrombosis represent one of the major goals in MPNs. The prothrombotic phenotype of MPNs is the result of a complex interplay between several components. Neutrophils, platelets, red blood cells (RBCs) and endothelial cells assume an activated phenotype in MPNs and undergo morphologic and metabolic changes that render these cells prothrombotic. These changes are in part the result of alterations induced by MPN initiating, driving mutations as well as the effect of extrinsic factors that stem from cell interactions as well as the inflammatory environment and rheological properties that characterize MPNs. In this review, we address current management issues in MPNs and provide an update on recent understanding of the pathogenesis of thrombosis in MPNs. We also address how lessons learned from other thrombo-inflammatory conditions can further inform and improve management of thrombosis in MPNs. Based on the above data and recent discoveries and developments, we discuss potential novel targets and therapeutic approaches to tackle the challenge of thrombosis in MPNs.

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Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia

Cited by 37 publications

References 41 publications

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Proteomics: A Tool to Study Platelet Function

Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?

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