REGULATION OF MONOCYTE TISSUE FACTOR ACTIVITY BY ALLOGENEIC AND XENOGENEIC ENDOTHELIAL-CELLS

The regulation of tissue factor (TF) activity by the cell associated t issue factor pathway inhibitor (TFPI) during monocyte (Mo) and endothe lial cell (EC) interactions is not fully understood. This report descr ibes co-ordinate induction of TF antigen (TF-Ag) and membrane-associat ed TFPI-Ag on human Mo following coculture with human aortic (HAEC) or porcine aortic EC (PAEC) or after stimulation with TNF alpha. We show that both allo- and xenogeneic EC induce human Mo-TF antigen in short -term culture. However, the TF activity of TNF alpha-primed Mo is supp ressed when these cells are cocultured with HAEC [by 40.3 +/- 6.3% (p< 0.02)] or PAEC [by 50.5 +/- 10.6% (p<0.001)]. Antibody (Ab) blocking s tudies confirm that TFPI is the principal anticoagulant associated wit h this suppression of TF-activity. Our data indicate that anti-TF acti vity originates, at least in part, from the activated human Mo in the coculture; additionally, specific generation of TFPI by Mo is observed under the xenogeneic culture conditions. As Mo associated TF, induced by allo- or xenogeneic EC interactions, is regulated by cell-associat ed TFPI, we propose that infiltrating Mo may modulate the thrombotic p rocess at sites of vascular injury in association with both allo-and x enograft rejection.