Thromb Haemost 1991; 66(05): 529-533
DOI: 10.1055/s-0038-1646454
Original Article
Schattauer GmbH Stuttgart

An Anti-Tissue Factor Monoclonal Antibody which Inhibits TF Vlla Complex Is a Potent Anticoagulant in Plasma

Wolfram Ruf
The Vascular Biology Group, Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA, USA
,
Thomas S Edgington
The Vascular Biology Group, Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 17. August 1990

Accepted 24. April 1991

Publikationsdatum:
25. Juli 2018 (online)

Summary

Tissue factor (TF) functions as the receptor and cofactor for factor VIIa (VIIa) to form a proteolytically active TFVIIa complex on cell surfaces. We here demonstrate that most MAbs against human TF were poor inhibitors of TF function in plasma and that they inhibited preformed TF-VIIa complex at a slow rate which was dependent on dissociation of VIIa from the cell surface TF. An exception was defined by one MAb (TF8-5G9) which was an effective immediate anticoagulant in plasma. Binding of TF8-5G9 to TF-VIIa inhibited catalytic function prior to dissociation of the TF-VIIa complex. This analysis thus establishes two distinct mechanisms by which MAbs interfere with TF function. The MAb TF8-5G9 introduces a therapeutic principle for rapid arrest of inappropriate triggering of coagulation by TF as well as the TF-VIIa complex in vivo.