title: Impaired coagulation of fibrinogen due to digestion of the C-terminal end of the A alpha-chain by human neutrophil elastase.
abstract: Human neutrophil elastase (HNE) possesses fibrinogenolytic capacity, with a high susceptibility towards degradation of the A alpha-chain. To study the influence of HNE digestion of the A alpha-chain on the coagulation 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 obtained with SDS electrophoresis and Western blotting with subsequent immunostaining, using monoclonal antibodies against the N-terminal end and C-terminal half of the A alpha-chain. Apparently, initial HNE digestion of the fibrinogen molecule occurred from the C-terminal end of the A alpha-chain, and was associated with prolongation of the TCT. With further 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 coagulation of fibrinogen.
authors.affiliation: Hematological Research Laboratory, Ullevål Hospital, University of Oslo, Norway.
authors.forename: E T
authors.initials: ET
authors.lastname: Bach-Gansmo
authors.forename: S
authors.initials: S
authors.lastname: Halvorsen
authors.forename: H C
authors.initials: HC
authors.lastname: Godal
authors.forename: O H
authors.initials: OH
authors.lastname: Skjønsberg
mesh_terms: D000595:Amino Acid Sequence; D001778:Blood Coagulation Disorders / Q000097:blood*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase
chemical_list: D005340:Fibrinogen; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase