Fasciola Hepatica Cathepsin L Proteinase Cleaves Fibrinogen and Produces a Novel Type of Fibrin Clot

• DOI: 10.1111/j.1432-1033.1995.tb20805.x
• Publication Date: 2005-03-04T12:38:50Z
• Authors: Andrew J. Dowd; Sharon McGonigle; John P. Dalton
• Keywords: 0301 basic medicine; Fibrin; Cathepsin L; Fibrinogen; Fasciola hepatica; Hirudins; Cathepsins; Peptide Mapping; Cysteine Endopeptidases; 03 medical and health sciences; Endopeptidases; Animals; Cattle

A cathepsin L proteinase secreted by the parasitic helminth Fasciola hepatica can cleave fibrinogen and produce a fibrin clot with a specific activity of 4.7 National Institutes of Health thrombin‐equivalent U/mg. This is the first report of a fibrinogen‐clotting activity aside that of thrombin and the snake venom proteinases, which are all serine proteinases. Clot formation by cathepsin L is not inhibited by the thrombin inhibitor hirudin or by the anti‐polymerant H‐Gly‐Pro‐Arg‐Pro‐OH. The enzyme exerts its activity on fibrinogen in a unique manner. Although the cleavage of fibrinogen may involve the initial removal of fibrinopeptides, additional proteolysis of the α, β and γ fibrinogen polypeptides takes place. SDS/PAGE analysis of the cathepsin‐l‐produced clots revealed that cleavage of the α polypeptide (66kDa) precedes that of the β (52kDa) and γ (46.5kDa) polypeptides. Concurrent with the cleavage of these polypeptides is the appearance of components of 120, 100 and 25 kDa. The appearance of higher molecular‐sized components in the cathepsin L clots suggests that polymerisation involves the formation of molecular interactions that are resistant to boiling in mercaptoethanol and SDS.