title: Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation.
abstract: BACKGROUND
  Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of factor XIII (FXIII), fibrinogen, prothrombin, and thrombin-activatable fibrinolysis inhibitor (TAFI) in plasma-based systems, and to analyse effects of MASP-1 on plasma clot formation, structure and lysis.
  
  
  RESULTS
  We used a FXIII incorporation assay and specific assays to measure the activation products prothrombin fragment F1+2, fibrinopeptide A (FPA), and activated TAFI (TAFIa). Clot formation and lysis were assessed by turbidimetric assay. Clot structure was studied by scanning electron microscopy. MASP-1 activated FXIII and, contrary to thrombin, induced FXIII activity faster in the Val34 than the Leu34 variant. MASP-1-dependent generation of F1+2, FPA and TAFIa showed a dose-dependent response in normal citrated plasma (NCP), albeit MASP-1 was much less efficient than FXa or thrombin. MASP-1 activation of prothrombin and TAFI cleavage were confirmed in purified systems. No FPA generation was observed in prothrombin-depleted plasma. MASP-1 induced clot formation in NCP, affected clot structure, and prolonged clot lysis.
  
  
  CONCLUSIONS
  We show that MASP-1 interacts with plasma clot formation on different levels and influences fibrin structure. Although MASP-1-induced fibrin formation is thrombin-dependent, MASP-1 directly activates prothrombin, FXIII and TAFI. We suggest that MASP-1, in concerted action with other complement and coagulation proteins, may play a role in fibrin clot formation.
authors.affiliation: Department of Internal Medicine, Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hess
authors.forename: Ramzi
authors.initials: R
authors.lastname: Ajjan
authors.forename: Fladia
authors.initials: F
authors.lastname: Phoenix
authors.forename: József
authors.initials: J
authors.lastname: Dobó
authors.forename: Péter
authors.initials: P
authors.lastname: Gál
authors.forename: Verena
authors.initials: V
authors.lastname: Schroeder
mesh_terms: D019943:Amino Acid Substitution; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000378:metabolism; D004789:Enzyme Activation; D005176:Factor XIII / Q000235:genetics / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism / Q000502:physiology*; D009391:Nephelometry and Turbidimetry; D059748:Proteolysis; D011516:Prothrombin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D011516:Prothrombin; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D025901:Carboxypeptidase B2; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases