Platelet-derived microvesicles transfer tissue factor to monocytes but not to neutrophils

Abstract

Activated platelets are known to adhere to both blood monocytes and neutrophils, and this adhesion is mainly mediated by the surface exposure of the platelet granule protein CD62P. Platelets as well as platelet-derived microvesicles (PMV) have also been shown to contain and to transfer tissue factor (TF), the most important initiator of intravascular thrombin and fibrin formation, to monocytes. However, the role of neutrophils for gathering platelet-derived TF is controversial. Here we studied the interaction of PMV with monocytes and neutrophils using a whole blood system. Platelet-rich plasma (PRP) obtained from citrated human blood was incubated with collagen (5 microg/ml, 15 min) and the platelets were removed by centrifugation (5 min at 5000 x g). After incubating the PMV-containing plasma for further 30 min with a sediment of red and white bloods cells that had been obtained after PRP preparation, monocytes and neutrophils were analysed by flow cytometry for the surface exposure of the platelet-specific antigen CD42a and TF. Compared to a control with non-activated PRP, there was a significant increase in the number of both CD42a-positive monocytes and neutrophils. In contrast, there was no change in the number of TF-positive neutrophils, but a more than 2-fold increase in the number of TF-positive monocytes. The changes in CD42a on monocytes and neutrophils as well as the changes in TF on monocytes could be significantly reduced by an anti-CD62P antibody or by removal of PMV from the plasma samples. The data indicate that the transfer of TF to monocytes is not simply an CD62P-mediated adhesion of platelets or PMV to monocytes, but may involve other not yet identified mechanisms.

The Influence of Exogenous Tissue Factor on the Regulators of Proliferation and Apoptosis in Endothelial Cells

“…This includes TF expressed by monocytes, granulocytes and platelets, TF-containing microparticles and truncated circulating TF. The transfer of TF between cells has been documented previously [11,12,13]. Also recently it has been suggested that there is cross-talk and interaction with other receptors [14], even suggesting an integrin-binding domain within TF.…”

Microvesicles: mediators of extracellular communication during cancer progression

“…Microvesicles shed from neurons and astrocytes contain growth factors and promote paracrine responses (Proia et al, 2008;Schiera et al, 2007). In addition, membrane proteins on microvesicles have been shown to interact specifically with molecules on target cells to promote signaling responses (Eken et al, 2008;Gasser et al, 2003;Losche et al, 2004;Pluskota et al, 2008). In some cases, direct binding results in fusion of the microvesicle with the target cell or endocytosis of the microvesicle.…”

Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers

“…2). Microvesicle-target cell interaction results in either the fusion of the microvesicle with the target cell or endocytosis of the microvesicle (Gasser et al 2003;Losche et al 2004;Eken et al 2008;Pluskota et al 2008). Here we discuss recent advances and speculations as to how individual sets of bioactive effectors-namely, proteins and nucleic acids-contained in TMVs can affect cancer progression.…”