Date of Award

Spring 1999

Document Type

Restricted Thesis

Terms of Use

© 1999 Robert S. Griffin. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Sara Hiebert Burch

Abstract

Plasminogen can bind to tissue factor in an interaction that enhances plasminogen activation but inhibits fibrinolysis. This observation suggests two hypotheses. First, the possibility that plasminogen can inhibit TF-VIIa dependent activation of factor X was tested. The activity of soluble TF-VIIa complexes (20 pM) toward factor X (100 nM) was not affected by plasminogen. In addition, plasminogen below 100 nM did not affect the rate of activation of factor X by VIIa bound to TF expressed by stably transfected CRO cells. These data suggest that plasminogen leaves TF-VIIa activity unaltered. Second, the possibility that TF and plasmin can promote the activation of factor X was tested. An enhanced rate of factor X activation was observed in the presence of both plasmin and cell-surface expressed TF as compared to the absence of either plasmin or TF. In addition, this enhancement of the factor X activation rate was dependent on plasmin concentration. Inactivation of plasmin with α2-antiplasmin and removal of TF from the cell surface both reduced the observed rate enhancement. These data suggest a mechanism in which plasmin and TF can together promote the activation of factor X. When considered in light of other evidence regarding plasmin-dependent activation of coagulation factors, the present results also suggest that plasmin activity may result in transient activation of the coagulation cascade.

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