DEGRADATION OF THE ALPHA-CHAIN OF FIBRIN BY HUMAN NEUTROPHIL ELASTASEREDUCES THE STIMULATING EFFECT OF FIBRIN ON PLASMINOGEN ACTIVATION

The degradation of fibrin by human neutrophil elastase (HNE) and the i nterference of such degradation on the stimulating effect of fibrin on plasminogen activation by tissue plasminogen activator (1-PA) was stu died. By using SDS electrophoresis and Western blotting with subsequen t immunostaining with monoclonal antibodies, degradation. of the fibri n molecule was monitored. This degradation was related to the stimulat ing effect on plasminogen activation. Degradation of the alpha-chain w as seen to occur before degradation of the beta- and gamma-chains. On the alpha-chain it was found that C-terminal degradation occurred prio r to visible degradation of the N-terminal end. This C-terminal degrad ation was associated with a fall in the stimulation of plasminogen act ivation, coinciding with a corresponding reduction in the polymerizati on of fibrin. With further degradation, including N-terminal proteolys is of the alpha-chain, the stimulating effect of fibrin was reduced to that of fibrinogen. Conclusions: Our results indicate that HNE degrad ation of the alpha-chain of fibrin occurs initially from the C-termina l end, affecting the polymerization of fibrin. This impaired polymeriz ation may be important for the observed reduction in the t-PA mediated plasminogen activation.