Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation

PLoS One. 2012;7(4):e35690. doi: 10.1371/journal.pone.0035690. Epub 2012 Apr 20.


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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Blood Coagulation Factors / metabolism
  • Blood Coagulation*
  • Carboxypeptidase B2 / metabolism
  • Enzyme Activation
  • Factor XIII / genetics
  • Factor XIII / metabolism*
  • Fibrin / metabolism
  • Fibrinogen / metabolism
  • Humans
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases / physiology*
  • Nephelometry and Turbidimetry
  • Proteolysis
  • Prothrombin / metabolism


  • Blood Coagulation Factors
  • Prothrombin
  • Fibrin
  • Fibrinogen
  • Factor XIII
  • Carboxypeptidase B2
  • MASP1 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases