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J Thromb Haemost. 2011 Nov;9(11):2251-61. doi: 10.1111/j.1538-7836.2011.04488.x.

Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability.

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1
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.

Abstract

BACKGROUND:

Microparticles (MPs) are sub-micron vesicles shed by activated or apoptotic cells, including platelets and monocytes. Increased circulating MPs are associated with thrombosis; however, their role in thrombogenesis is poorly understood.

OBJECTIVE:

To determine how MPs promote thrombin generation and modulate fibrin density and stability.

METHODS:

Platelets and monocytes were isolated from healthy donors. Platelets were stimulated with calcium ionophore, thrombin receptor agonist peptide (TRAP) or TRAP/convulxin. Monocytes and human monocytic THP-1 cells were stimulated with lipopolysaccharide (LPS). MPs were isolated, washed by high-speed centrifugation and assessed using the following: transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA), flow cytometry, tissue factor (TF) activity, prothrombinase activity, thrombin generation, and clot formation, density and stability.

RESULTS:

MPs from monocytes (M-MPs) and platelets (PMPs) had similar shapes and diameters (100-300 nm). M-MPs had TF activity (16.7 ± 2.4 pm TF per 10(6) MP), supported prothrombinase activity and triggered shorter thrombin generation lag times than buffer controls (5.4 ± 0.5 vs. 84.2 ± 4.8 min, respectively). Compared with controls, M-MPs supported faster fibrin formation (0.24 ± 0.24 vs. 76.7 ± 15.1 mOD min(-1) , respectively), 38% higher fibrin network density and higher clot stability (3.8-fold higher turbidity in the presence of tissue plasminogen activator). In contrast, PMPs did not have TF activity and supported 2.8-fold lower prothrombinase activity than M-MPs. PMPs supported contact-dependent thrombin generation, but did not independently increase fibrin network density or stability. Interestingly, PMPs increased rates of thrombin generation and fibrin formation (1.7- and 1.3-fold, respectively) when mixed with THP-1-derived MPs.

CONCLUSION:

MPs from platelets and monocytes differentially modulate clot formation, structure and stability, suggesting unique contributions to thrombosis.

PMID:
21883880
PMCID:
PMC3206146
DOI:
10.1111/j.1538-7836.2011.04488.x
[Indexed for MEDLINE]
Free PMC Article
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