THE EFFECT OF CELL-SURFACE GLYCOSAMINOGLYCANS (GAGS) ON THE INACTIVATION OF FACTOR VIIA TISSUE FACTOR ACTIVITY BY ANTITHROMBIN-III

We investigated the effect of cell surface glycosaminoglycans (GAGs) o n the inactivation of factor VIIa-tissue factor activity by antithromb in III (ATIII) on a human bladder carcinoma (J82) cell line and an ova rian carcinoma (OC-2008) cell line, two tumor cell lines which constit utively synthesize and express high levels of cell surface tissue fact or. We observed that ATIII inactivated factor VII-tissue factor more r eadily on OC-2008 cells than on J82 cells in the absence of added hepa rin. Likewise, factor Xa was more effectively inactivated on OC-2008 c ells than on J82 cells. The ability of ATIII to inactivate factor VIIa -tissue factor activity on the OC-2008 cell was reduced following trea tment of the cells with heparinase. This indicated that heparin-like G AGs were expressed on the OC-2008 cell surface, and that these GAGs we re important for the inhibition of factor VIIa-tissue factor activity by ATIII. In addition, we demonstrated that the ability of ATIII to in activate factor VIIa-tissue factor activity was markedly reduced follo wing treatment of cells with calcium ionophore (A23187). However. the effect of cell surface GAGs on the inhibition of factor Xa by ATIII re mained even after treatment of OC-2008 cells with A23187. In contrast to the manner of inhibition by ATIII/heparin, TFPI effectively inactiv ated factor VIIa-tissue factor activity on the cell surfaces even afte r induced physical damage or disruption of the cell by treatment with A23187. Our collective findings suggest that GAGs on cell surfaces pla y an important role in regulating factor VIIa-tissue factor activity b y ATIII under normal conditions, or in the early phases of physical da mage or destruction of the cell. However, TFPI may play a more importa nt role than ATIII in regulating the activity of factor VIIa-tissue fa ctor in a vascular trauma site following extensive cell injury. (C) 19 98 Elsevier Science Ireland Ltd. All rights reserved.