The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation. (15th February 2016)

• Record Type: Journal Article
• Authors: Kozarcanin, H.; Lood, C.; Munthe‐Fog, L.; Sandholm, K.; Hamad, O. A.; Bengtsson, A. A.; Skjoedt, M.‐O.; Huber‐Lang, M.; Garred, P.; Ekdahl, K. N.; Nilsson, B.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 14:Number 3(2016:Mar.)
• Page Start: 531
• Page End: 545
• Publication Date: 2016-02-15
• Subjects: blood coagulation -- complement pathway -- mannose‐binding lectin -- fibrin -- mannose‐binding protein‐associated serine proteases -- platelet activation; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13208
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials The lectin pathway's MASP‐1/2 activates coagulation factors but the trigger of the activation is unknown. MASP‐1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1‐inhibitor. Activated platelets and fibrin were demonstrated to activate MASP‐1 and MASP‐2 both in vitro and in vivo . These findings may represent a crossroad between the complement and the coagulation systems. Summary: Background: The activated forms of the complement lectin pathway (LP) proteases MASP‐1 and MASP‐2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin‐activatable fibrinolysis inhibitor in vitro . In vivo studies also show that MASP‐1 is involved in thrombogenesis. Objectives: To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods: Novel sandwich‐ELISAs for detection of complexes between MASP‐1 or MASP‐2 and the serpins C1 inhibitor (C1‐INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP‐1 and MASP‐2. Results: Activated platelets were shown by flow cytometry to bind Ficolin‐1, ‐2 and ‐3 but not MBL, which was associated with activation of MASP‐1 and MASP‐2. We also demonstrated that fibrin and the plasmin‐generated fibrin fragment DD in plasma, bind and activate MASP‐1 and MASP‐2. As demonstrated by the ELISA and SDS‐PAGE/Western blotting, the fibrin‐associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1‐INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP‐1 and MASP‐2 in complex with both AT and C1‐INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions: MASP‐1 and MASP‐2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions in vitro and in vivo, and may represent a novel activation/amplification mechanism in thromboinflammation.