Enhancement of Plasminogen Binding to U937 Cells and Fibrin by Complestatin

Summary

Plasminogen binds to endothelial and blood cells as well as to fibrin, where the zymogen is efficiently activated and protected from inhibition by α₂-antiplasmin. In the present study we have found that complestatin, a peptide-like metabolite of a streptomyces, enhances binding of plasminogen to cells and fibrin. Complestatin, at concentrations ranging from 1 to 5 μM, doubled ¹²⁵I-plasminogen binding to U937 cells both in the absence and presence of lipoprotein(a), a putative physiological competitor of plasminogen. The binding of ¹²⁵I-plasminogen in the presence of complestatin was abolished by e-aminocaproic acid, suggesting that the lysine binding site(s) of the plasminogen molecule are involved in the binding. Equilibrium binding analyses indicated that complestatin increased the maximum binding of ¹²⁵I-plasminogen to U937 cells without affecting the binding affinity. Complestatin was also effective in increasing ¹²⁵I-plasminogen binding to fibrin, causing 2-fold elevation of the binding at ~1 μM. Along with the potentiation of plasminogen binding, complestatin enhanced plasmin formation, and thereby increased fibrinolysis. These results would provide a biochemical basis for a pharmacological stimulation of endogenous fibrinolysis through a promotion of plasminogen binding to cells and fibrin.

• References

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