Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells

Abstract

: Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

Coagulation and fibrinolysis in gastric cancer

“…In recent years, there has been a growing interest in the potential role of tumor‐derived TF + MPs in the processing governing VTE . MPs are small membrane vesicles released into the blood from activated or apoptotic cells, including platelets, monocytes, granulocytes, and endothelial cells, with a different procoagulant activity depending on the cells of origin . The first characterized property of MPs is the ability to support thrombin generation .…”

“…150 MPs are small mem-brane vesicles released into the blood from activated or apoptotic cells, including platelets, monocytes, granulocytes, and endothelial cells, with a different procoagulant activity depending on the cells of origin. 79,151 The first characterized property of MPs is the ability to support thrombin generation. 153 Tumor cells were found to spontaneously release elevated levels of tumor-derived TF + MPs into the blood, and this event correlated with an increase in venous thrombosis in mouse models and cancer patients.…”

Platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation

“…Variations in the percentage of annexin V-positive MPs could be at least partially explained by the difference in MPs size. Earlier, using the dynamic light scattering method, for the MPs sizing, we have shown in direct comparative studies that ErMPs have an average diameter of 200-250 nm, PMPs 350-400 nm, EMPs and THP MPs 400-500 nm, and EMPs 550-600 nm [29,30,47]. We presumed that annexin V-FITC binding to small MPs was too low to provide FITC signals above the threshold noise level, which is why we measured the different percentages of annexin V-positive events in samples of MPs of different origins with different average sizes.…”

“…Microparticles (MPs) produced by activated platelets, monocytes, human monocytic THP-1 cells and endothelial cells (ECs) were prepared as described earlier in detail [29, 31]. Platelets and monocytes were isolated from the blood of healthy volunteers.…”

Update on pathological platelet activation in coronary thrombosis

“…Negatively charged phosphatidylserine expressed on PMV surface provides a catalytic surface for factor X and prothrombin activation, which are essential for the coagulation process(Melki, Tessandier, Zufferey, & Boilard, 2017). Moreover, PMVs combine with TF and secrete plasminogen activator inhibitor-1, thus further enhancing the blood clot formation(Shustova et al, 2017). Hence, higher concentrations of PMVs are generated in CT, transient ischemic attacks and strokes, and peripheral arterial disease(Zaldivia et al, 2017).Noteworthily, PMVs contain and express some important factors or receptors that play an active role in the crosstalk with leukocytes.Mechanistically, PMV-leukocyte aggregates induce the release of proinflammatory mediators through their content of immunoglobulins, antigens, cytokines, and chemokines.…”