Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: Studies using a new digital flow cytometer

Pérez-Pujol, Sı́lvia; Marker, Paul H.; Key, Nigel S.

doi:10.1002/cyto.a.20354

Cited by 148 publications

(134 citation statements)

References 51 publications

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“…43 However, exosomes do not express phosphatidylserine on their surface, 23 which is consistent with the fact that the Del-1 antibody does not inhibit their uptake by endothelium. Activated platelets and endothelial cells also generate a significant proportion of microparticles that do not express phosphatidylserine, 44,45 and the clearance of these microparticles will be Del-1 independent.…”

Section: Dasgupta Et Al Del-1 and Microparticle Clearancementioning

confidence: 99%

Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium

et al. 2012

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Background-Phosphatidylserine-expressing microparticles circulate in blood with a short half-life of Ͻ10 minutes. We tested the role of an endothelium-derived phosphatidylserine-binding opsonin, developmental endothelial locus-1 (Del-1), in the uptake of platelet microparticles. Methods and Results-Cultured human umbilical vein and microvascular endothelial cells avidly engulf BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-maleimide-labeled platelet microparticles. Microparticle uptake was inhibited by a monoclonal antibody to Del-1 (Pϭ0.027) and by annexin A5 (Pϭ0.027), abciximab (Pϭ0.027), a monoclonal antibody to integrin ␣V␤3 (Pϭ0.027), and chlorpromazine (Pϭ0.027). These results suggest that Del-1 mediates phosphatidylserine-and integrin-dependent endothelial uptake of microparticles by endocytosis. To assess the in vivo significance, we infused fluorescent platelet microparticles into the inferior vena cava of mice and harvested endothelial cells from the pulmonary and systemic circulation. Compared with their wild-type littermates, Del-1-deficient mice had decreased uptake in endothelial cells in lung (3.07Ϯ1.9 versus 1.09Ϯ1.

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Section: Dasgupta Et Al Del-1 and Microparticle Clearancementioning

confidence: 99%

Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium

et al. 2012

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“…These strands, called flow-induced protrusions, also expose PS, recruit neutrophils and monocytes (and not platelets), and appear to break off into PS + microparticles (114). Intriguingly, studies also shed light on PS 2 microparticles in body fluids (111,(115)(116)(117), pointing to the heterogeneity of the microparticles produced by platelets. The small dimensions of microparticles represent a challenge for the proper assessment of their expression in biological fluids.…”

Section: Platelet Microparticlesmentioning

confidence: 99%

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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“…After finding a mean of2 10 5 CD41 + MPs per microliter of synovial fluid from 20 RA patients, detectable levels in only 1/20 synovial fluid from patients with osteoarthritis, their pathophysiological significance in inflammatory arthritis was studiedin vivo in mouse [48]. Collagen-activated platelets can form MPs (distinct from intact platelets) [49]. These platelets predominantly express glycoprotein VI (GPVI) (collagen receptor) [48] which, when activated generates these MPs [50].…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Microparticles and their Roles in Inflammation: A Review§

Batool¹,

Abbasian²,

Burton

et al. 2013

TOIJ

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Microparticles (MPs) were long dismissed as "platelet-dust", cell debris, with no functional significance. Theyare anucleated vesicles (0.1μm to 1μm), enclosed in a membrane, secretedinto the circulation by cells during cell activation or apoptosis. They have now emerged as mediators and markers of inflammatory diseases and autoimmune disorders. They are distinctly different from exosomes and apoptotic bodiesand are released from nearly every cell type, the most abundant being platelets, leukocytes and endothelial cells. MPs can be detected using flow cytometry and more recently by nanotechnology, which is more accuratein detecting, quantifying and phenotypingMPs.MPs are instrumental in the pathogenesis of various cardiovascular diseases (thrombotic and atherosclerotic) through their pro-inflammatory and pro-coagulant properties. Their levels are significantly elevated in chronic inflammatory disorders such as rheumatoid arthritis and multiple sclerosis. However, increasing evidence suggests they also possess antiinflammatory and anti-coagulant roles which could confer immunoprotection. MPs transport various lipids, proteins, mRNA and microRNA (miRNA) which may influence activities of receiving cells. Particularly the miRNAspecies delivered by MPs have been shown to modulate inflammation.In vitro and in vivo studies are being conducted to bioengineer MPs to facilitate delivery of therapeutic compounds to desired location safely, specifically and more effectively, with fewer side effects. More research is required to understand the composition, origin, mechanisms of formation and release as well as their clearance from the circulation to pave way for gaining greater pharmacological benefits by controlling MP-mediated cellular responses.

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Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: Studies using a new digital flow cytometer

Cited by 148 publications

References 51 publications

Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium

Developmental Endothelial Locus-1 (Del-1) Mediates Clearance of Platelet Microparticles by the Endothelium

Nouvelle Cuisine: Platelets Served with Inflammation

Microparticles and their Roles in Inflammation: A Review§

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