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 t issue factor (TF) expression was investigated using the cultured human mono blastic leukemia U937 cell line. A flow cytofluorometric analysis demonstra ted that treatment with APC resulted in time- and dose-dependent decrease i n TF expression in unstimulated and phorbol ester-stimulated cells. The eff ect was antagonized by the monoclonal antibody (mAb) to endothelial protein C/APC receptor (EPCR), 252, which strongly inhibited the interaction betwe en APC and EPCR, In contrast, mAbs 49 and 379, which bind to EPCR without b locking APC binding, had no or only a modest effect. It is concluded that c ulturing U937 cells in the presence of APC caused down-regulation of TF exp ression through the EPCR-dependent mechanism, independent of whether induct ion was triggered by phorbol ester, (C) 2000 Federation of European Biochem ical Societies. Published by Elsevier Science B.V. All rights reserved.