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Updated: Aug 9, 2026

Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
Activated protein C suppresses tissue factor expression on U937 cells in the endothelial protein C receptor-dependent
F Shua1, H Kobayashia, K Fukudomeb
1Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract:
The new functional role of activated protein C (APC) in the regulation of tissue factor (TF) expression was investigated using the cultured human monoblastic leukemia U937 cell line. A flow cytofluorometric analysis demonstrated that treatment with APC resulted in time- and dose-dependent decrease in TF expression in unstimulated and phorbol ester-stimulated cells. The effect was antagonized by the monoclonal antibody (mAb) to endothelial protein C/APC receptor (EPCR), 252, which strongly inhibited the interaction between APC and EPCR. In contrast, mAbs 49 and 379, which bind to EPCR without blocking APC binding, had no or only a modest effect. It is concluded that culturing U937 cells in the presence of APC caused down-regulation of TF expression through the EPCR-dependent mechanism, independent of whether induction was triggered by phorbol ester.
Insights
Activated protein C (APC) down-regulates tissue factor (TF) expression in U937 leukemia cells. This effect is mediated via the endothelial protein C/APC receptor (EPCR) and occurs independently of stimulation.
Area of Science:
- Hematology
- Molecular Biology
- Cell Biology
Background:
- Tissue factor (TF) initiates the coagulation cascade.
- Activated protein C (APC) is a known anticoagulant.
- The role of APC in regulating TF expression is not fully understood.
Purpose of the Study:
- To investigate the functional role of APC in regulating TF expression.
- To elucidate the mechanism by which APC affects TF expression.
Main Methods:
- Cultured human monoblastic leukemia U937 cell line.
- Flow cytofluorometric analysis.
- Monoclonal antibodies (mAbs) targeting EPCR.
Main Results:
- APC treatment decreased TF expression in a time- and dose-dependent manner.
- An EPCR-blocking mAb (252) antagonized APC's effect on TF.
- Non-blocking EPCR mAbs (49, 379) had minimal effect.
Conclusions:
- APC down-regulates TF expression in U937 cells.
- This regulation occurs via an EPCR-dependent mechanism.
- APC's effect on TF is independent of phorbol ester stimulation.
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