Aleman, MM;
Gardiner, C;
Harrison, P;
Wolberg, AS;
(2011)
Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability.
Journal of Thrombosis and Haemostasis
, 9
(11)
pp. 2251-2261.
10.1111/j.1538-7836.2011.04488.x.
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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.
Type: | Article |
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Title: | Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1111/j.1538-7836.2011.04488.x |
Publisher version: | http://doi.org/10.1111/j.1538-7836.2011.04488.x |
Language: | English |
Keywords: | fibrinogen, microparticle, phosphatidylserine, thrombosis, tissue factor |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1468247 |
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