High‐affinity binding sites for human Glu‐plasminogen unveiled by limited plasmic degradation of human fibrin

Abstract

The binding of human 125I‐Glu‐plasminogen to human plasmin‐degraded fibrin was studied. Treatment of preformed and polymerized fibrin with 0.01 IU plasmin/ml resulted in an increased binding of 125I‐Glu‐plasminogen depending upon the length of time of preincubation of fibrin with plasmin. Binding reached a plateau of 30% of total added radioactivity after 60 min. At this time, less than 10% of fibrin had been digested. Polyacrylamide/urea/acetic acid gel electrophoresis revealed that the radioiodinated plasminogen bound to plasmin‐degraded fibrin was of the Glu form. Computerized non‐linear regression analysis of the binding experiments revealed that limited plasmic degradation of fibrin progressively generates high‐affinity binding sites (Kd∼ 0.3 μM) for Glu‐plasminogen. At the time of maximal Glu‐plasminogen binding approximately 5 high‐affinity binding sites per 100 molecules of fibrin had been generated. The low‐affinity type of binding sites were also identified. These observations describe a new mechanism which exquisitely modulates the plasmic breakdown of fibrin by a continuous renewal of high‐affinity binding sites for Glu‐plasminogen on the surface of the fibrin gel during the fibrinolytic process. Copyright © 1986, Wiley Blackwell. All rights reserved