Summary
This study demonstrates that poly-lysine mimics the cofactor (enhancing) function of fibrin that is seen in tissue activator-induced plasminogen activation. Additionally, and in contrast to fibrin, poly-lysine exhibited an enhancing effect on low molecular weight (and not high molecular weight) urokinase-induced plasminogen activation.
A mechanism is proposed for this enhancement that involves the rendezvous and local concentration of plasminogen and plasminogen activator molecules on the lysine polymer. All components were able to bind to immobilized poly-lysine making the proposed machanism feasible. It was possible to elute the activators and mini-plasminogen by high salt (1 M NaCl), in contrast to Glu-plasminogen and plasmin which required 1 M lysine for elution, suggesting specific binding involving lysine binding sites.
The enhancing effect was specific for poly-D- and L-lysine and poly-L-ornithine, which has a similar structure. The use of poly-lysine can lead to a better standardization and increased sensitivity of indirect two-step assays for plasminogen activators employing synthetic chromogenic substrates.
Key words
Plasminogen activation - Urokinase - Tissue plasminogen activator - Poly-lysine - Enhancement of plasminogen activation - Plasminogen activator assay - Lysine binding site
