Apoptosis is associated with increased cell surface tissue factor procoagulant activity

Tissue factor (TF), the physiologic initiator of coagulation, is present on the surface of cells but is not fully active unless the cell is lysed. This phenomenon, termed TF encryption, may be regulated by changes in membrane structure. Because apoptosis is associated with cell membrane alterations and conditions associated with apoptosis have also been associated with TF de-encryption, we hypothesized that apoptosis would result in enhanced TF procoagulant activity. Cultured human fibroblasts and endotoxin-stimulated endothelial cells were treated to induce apoptosis as evidenced by morphologic and DNA changes. Under the same conditions, changes in the level of TF activity were measured. Conditions that resulted in endothelial apoptosis were associated with de-encryption of TF activity. Similar results were obtained in fibroblasts except that only the morphologic changes, not the alterations in DNA size characteristic of apoptosis in other cells, were found. The data suggest an association between apoptosis and expression of cell surface tissue factor activity. Because of the recognized linkage of the coagulation system with wound healing and neoplasia, we speculate that this association may help to regulate the flux of cells in tissues being remodelled by apoptosis.