Megakaryocytes package contents into separate α-granules that are differentially distributed in platelets

Battinelli, Elisabeth M.; Thon, Jonathan N.; Okazaki, Ross; Peters, Christian; Vijey, Prakrith; Wilkie, Adrian R.; Noetzli, Leila; Flaumenhaft, Robert; Italiano, Joseph E.

doi:10.1182/bloodadvances.2018020834

Cited by 43 publications

(32 citation statements)

References 31 publications

(39 reference statements)

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“…Our results indicate that platelets with procoagulant phenotype are generated in COVID-19 patients, either in the peripheral circulation or from inflammation-programmed megakaryocytes. 36 , 40 Given the limitations due to safety protocols, requiring inactivation of the SARS-CoV-2 virus in biological samples, we could not obtain a more extensive characterization of procoagulant profile by measuring binding of annexin V to platelets expressing phosphatidylserine. 19 Previous studies indicate that P-selectin expression can be enhanced in vitro by strong agonists and through the engagement of integrins, and this is associated to a procoagulant phenotype and the release of microvesicles.…”

Section: Discussionmentioning

confidence: 99%

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Taus

Salvagno

Canè

et al. 2020

ATVB

150

182

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Objective: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P <0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P <0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P =nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients ( P <0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P <0.001), showed accelerated factor XII–dependent coagulation. Conclusions: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

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Section: Discussionmentioning

confidence: 99%

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Taus

Salvagno

Canè

et al. 2020

ATVB

150

182

View full text Add to dashboard Cite

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“…Activation signals from proteinase‐activated receptor (PAR)1 (thrombin receptor), adenosine diphosphate receptors, and glycoprotein VI favor the release of proangiogenic factors (eg, VEGF), whereas PAR4 and TxA2 promote anti‐angiogenic factor (eg, endostatin) release . Differential packaging of pro‐ and anti‐angiogenic proteins in distinct α‐granules in platelets has also been reported in addition to differential release upon platelet activation . Similar mechanisms may be applicable to lymphangiogenesis, in that pro‐ and antilymphangiogenic proteins are differently packed in distinct α‐granules and are differentially released upon platelet activation.…”

Section: Do Platelets Facilitate or Inhibit Lymphangiogenesis?mentioning

confidence: 95%

Crosstalk between hemostasis and lymphangiogenesis

Suzuki‐Inoue

Tsukiji

Otake

2020

Journal of Thrombosis and Haemostasis

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“…Platelet immune-secretory responses are much more complex than previously thought [ 25 ]. Granule contents are heterogeneous and show surprisingly little co-localization patterns [ 26 , 27 , 28 ], indicating distinct packaging of these factors to facilitate diversity in platelet function. Furthermore, distinct platelet agonists or stimulation lengths promote differential release of granule contents, which can induce opposing functions [ 29 , 30 , 31 ].…”

Section: Platelets and Their Complex Role In Inflammationmentioning

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

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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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Megakaryocytes package contents into separate α-granules that are differentially distributed in platelets

Abstract: Key Points Mouse megakaryocytes can differentially sort and package endocytosed fibrinogen and endostatin into distinct α-granules. Platelet progenitors contain subpopulations of α-granules.

Cited by 43 publications

References 31 publications

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Crosstalk between hemostasis and lymphangiogenesis

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

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