IMPAIRED COAGULATION OF FIBRINOGEN DUE TO DIGESTION OF THE C-TERMINALEND OF THE A-ALPHA-CHAIN BY HUMAN NEUTROPHIL ELASTASE

Human neutrophil elastase (HNE) possesses fibrinogenolytic capacity, w ith a high susceptibility towards degradation of the A alpha-chain. To study the influence of HNE digestion of the A alpha-chain on the coag ulation of fibrinogen by thrombin, fibrinogen was incubated with human neutrophil elastase (HNE). At intervals, thrombin clotting time (TCT) and clottability were determined and compared with the patterns obtai ned with SDS electrophoresis and Western blotting with subsequent immu nostaining using monoclonal antibodies against the N-terminal end and C-terminal half of the A alpha-chain. Apparently, initial HNE digestio n of the fibrinogen molecule occurred from the C-terminal end of the A alpha-chain, and was associated with prolongation of the TCT. With fu rther C-terminal degradation TCT became indefinite and the degradation products were no longer clottable. Finally, N-terminal degradation of the A alpha-chain was observed. The present observations suggest that initial HNE-digestion of fibrinogen occurs from the C-terminal end of the A alpha-chain, and that the C-terminal end is crucial for the coa gulation of fibrinogen.