Degradation of the alpha-chain of fibrin by human neutrophil elastase reduces the stimulating effect of fibrin on plasminogen activation.
The degradation of fibrin by human neutrophil elastase (HNE) and the interference of such degradation on the stimulating effect of fibrin on plasminogen activation by tissue plasminogen activator (t-PA) was studied. By using SDS electrophoresis and Western blotting with subsequent immunostaining with monoclonal antibodies, degradation of the fibrin molecule was monitored. This degradation was related to the stimulating effect on plasminogen activation. Degradation of the alpha-chain was seen to occur before degradation of the beta- and gamma-chains. On the alpha-chain it was found that C-terminal degradation occurred prior to visible degradation of the N-terminal end. This C-terminal degradation was associated with a fall in the stimulation of plasminogen activation, coinciding with a corresponding reduction in the polymerization of fibrin. With further degradation, including N-terminal proteolysis of the alpha-chain, the stimulating effect of fibrin was reduced to that of fibrinogen.


CONCLUSIONS
Our results indicate that HNE degradation of the alpha-chain of fibrin occurs initially from the C-terminal end, affecting the polymerization of fibrin. This impaired polymerization may be important for the observed reduction in the t-PA mediated plasminogen activation.
Bach-Gansmo
E T
ET
Hematological Research Laboratory, Ullevål Hospital, University of Oslo, Norway.
Halvorsen
S
S
Godal
H C
HC
Skjønsberg
O H
OH
D004789:Enzyme Activation / Q000187:drug effects; D005337:Fibrin / Q000737:chemistry* / Q000187:drug effects / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011108:Polymers; D013329:Structure-Activity Relationship; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D011108:Polymers; D005337:Fibrin; D010958:Plasminogen; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D010959:Tissue Plasminogen Activator