Abstract
BackgroundNumerous 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 FindingsWe 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/SignificanceWe 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.
Highlights
The coagulation and complement systems are activated following external injury to protect the host from blood loss and infections
Data on fibrin fiber diameters obtained from SEM of thrombin and mannan-binding lectin-associated serine protease-1 (MASP-1) clots were tested for normal distribution using the Kolmogorov-Smirnov test
factor XIII (FXIII) activation In a purified system with 20 mg/ml (62 nM) of FXIII, MASP-1 induced FXIII-dependent biotin incorporation in a dose-dependent manner, whereas no incorporation was observed without FXIII or in the presence of 100 mg/ml (1 mM) of C1 inhibitor (Fig. 1a)
Summary
The coagulation and complement systems are activated following external injury to protect the host from blood loss and infections. A number of recent studies show direct interactions between the two systems [2,3], among them are links between coagulation factors and mannan (or mannose) -binding lectin (MBL) associated serine proteases (MASPs) of the complement lectin pathway. The lectin pathway of the complement system is activated by binding of the target recognition molecules MBL or ficolins to carbohydrates or N-acetylated groups, respectively, on the surface of cells or microorganisms. Three MASPs and two related proteins are present in human plasma, arising from two genes by alternative splicing: Mannose-binding lectin-associated serine protease-1 (MASP-1) and its alternatively-spliced variants MASP-3 and MAp44, and MASP-2 and its alternatively-spliced variant MAp19. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
