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

Katharina Hess, Ramzi Ajjan, Fladia Phoenix, J. Dobó, P. Gál, Verena Schroeder

Research output: Contribution to journalArticle

52 Citations (Scopus)

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. 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.

Original languageEnglish
Article numbere35690
JournalPLoS One
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 20 2012

Fingerprint

Mannose-Binding Protein-Associated Serine Proteases
Complement C1
Mannose-Binding Lectin
Blood Coagulation Factors
Serine Proteases
serine proteinases
coagulation
lectins
complement
Chemical activation
Plasmas
thrombin
Carboxypeptidase B2
prothrombin
Prothrombin
Factor XIII
fibrinolysis
Fibrinopeptide A
fibrin
Coagulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. / Hess, Katharina; Ajjan, Ramzi; Phoenix, Fladia; Dobó, J.; Gál, P.; Schroeder, Verena.

In: PLoS One, Vol. 7, No. 4, e35690, 20.04.2012.

Research output: Contribution to journalArticle

Hess, Katharina ; Ajjan, Ramzi ; Phoenix, Fladia ; Dobó, J. ; Gál, P. ; Schroeder, Verena. / Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. In: PLoS One. 2012 ; Vol. 7, No. 4.
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