CLEC-2 expression is maintained on activated platelets and on platelet microparticles

Gitz, Eelo; Pollitt, Alice Y.; Gitz-Francois, Jerney J.; Alshehri, Osama M.; Mori, Jun; Montague, Samantha J.; Nash, Gerard B.; Douglas, Michael E.; Gardiner, Elizabeth E.; Andrews, Robert K.; Buckley, Christopher D.; Harrison, Paul; Watson, Steve P.

doi:10.1182/blood-2014-05-572818

Cited by 108 publications

(117 citation statements)

References 66 publications

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“…For instance, levels of platelet-derived microparticles are increased in blood and synovial fluid of patients affected with rheumatoid arthritis (RA), the most common autoimmune joint disorder (8,(120)(121)(122)(123). Consistently, different groups found that platelet depletion in a murine model of RA attenuates inflammation (8,124).…”

Section: Platelet Microparticlesmentioning

confidence: 58%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

179

191

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Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

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Section: Platelet Microparticlesmentioning

confidence: 58%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

179

191

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“…They enhance vascular permeability and release MPs, which have been implicated in aiding the formation of immune complexes via autoantigen expression [68,69]. MPs were also found to be carriers of the C-type lectin-like receptor 2 (CLEC-2) as with the originating cells which enables cleavage of the platelet glycoprotein GPVI [70]. Whether this is required prior to activation via collagen binding is yet to be established.…”

Section: Platelet Contributions To Ra Pathologymentioning

confidence: 99%

Platelet and red blood cell interactions and their role in rheumatoid arthritis

Olumuyiwa-Akeredolu

Pretorius

2015

Rheumatol Int

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“…30,31 Plasma sGPVI reflects platelet activation in thrombotic conditions including microangiopathy, 32 stroke, 33 DIC, 33 and Alzheimer's disease 34 and rheumatoid arthritis. 28,35 However, elevated plasma sGPVI levels in these patient groups is surprising, as only a fraction of platelets would be exposed to collagen, FXa, or elevated shear, and neither FcgRIIA or CLEC-2 plays major roles in hemostasis/thrombosis. The recent finding that fibrin activates GPVI provides a plausible explanation for this increase.…”

Section: Introductionmentioning

confidence: 99%

“…sGPVI Enzyme-Linked Immunosorbent Assay sGPVI levels were measured by sandwich enzyme-linked immunosorbent assay, 28,30 and concentrations extrapolated from standard curves generated by serial dilution of GPVI ectodomain into 5% vol/vol GPVI-depleted plasma. 28 …”

Section: Washed Platelet Preparation and Experimentsmentioning

confidence: 99%

“…[22][23][24][25] GPVI shedding is induced by GPVI ligands including collagen, collagen-related peptide (CRP), and venom toxins, 23,24,26,27 and by engagement of other platelet ITAM receptors FcgRIIA and CLEC-2. 28,29 Elevated fluid shear stress and active factor X (FXa) also trigger GPVI shedding, quantified by detection of the soluble ectodomain fragment (sGPVI) in plasma by an enzyme-linked immunosorbent assay. 30,31 Plasma sGPVI reflects platelet activation in thrombotic conditions including microangiopathy, 32 stroke, 33 DIC, 33 and Alzheimer's disease 34 and rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

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Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

Montague

Delierneux

Lecut³

et al. 2018

Blood Advances

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• Soluble GPVI is elevated in patients with thermal injury with sepsis, and sGPVI levels augment severity score prediction of mortality.• The GPVI ligand, fibrin, induces GPVI shedding without requirement for platelet activation or signaling Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU)for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28-and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 59-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients.

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CLEC-2 expression is maintained on activated platelets and on platelet microparticles

Abstract: Key Points CLEC-2 activation induces proteolytic cleavage of GPVI and FcγRIIa but not itself. CLEC-2 but not GPVI is detected on platelet-derived microparticles.

Cited by 108 publications

References 66 publications

Nouvelle Cuisine: Platelets Served with Inflammation

Nouvelle Cuisine: Platelets Served with Inflammation

Platelet and red blood cell interactions and their role in rheumatoid arthritis

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

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