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.

FEBS Letters
|July 26, 2000
PubMed

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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