Activated protein C suppresses tissue factor expression on U937 cells in the endothelial protein C receptor-dependent manner.

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.