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- W2176278444 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: BackgroundThe 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.ObjectivesTo clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions.MethodsNovel 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.ResultsActivated 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.ConclusionsMASP‐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. 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. •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. 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. To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. 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. 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. 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." @default.
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- W2176278444 date "2016-03-01" @default.
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- W2176278444 title "The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation" @default.
- W2176278444 cites W1539511863 @default.
- W2176278444 cites W1814046987 @default.
- W2176278444 cites W1843905884 @default.
- W2176278444 cites W1965901007 @default.
- W2176278444 cites W1966702861 @default.
- W2176278444 cites W1970365484 @default.
- W2176278444 cites W1976444953 @default.
- W2176278444 cites W1984315653 @default.
- W2176278444 cites W1994164445 @default.
- W2176278444 cites W1999577950 @default.
- W2176278444 cites W2002927269 @default.
- W2176278444 cites W2011846108 @default.
- W2176278444 cites W2013559177 @default.
- W2176278444 cites W2015371417 @default.
- W2176278444 cites W2015690645 @default.
- W2176278444 cites W2016139174 @default.
- W2176278444 cites W2023682375 @default.
- W2176278444 cites W2030345149 @default.
- W2176278444 cites W2035537561 @default.
- W2176278444 cites W2035960879 @default.
- W2176278444 cites W2043922211 @default.
- W2176278444 cites W2054116891 @default.
- W2176278444 cites W2068089057 @default.
- W2176278444 cites W2072426213 @default.
- W2176278444 cites W2089135776 @default.
- W2176278444 cites W2092536645 @default.
- W2176278444 cites W2100345855 @default.
- W2176278444 cites W2105614022 @default.
- W2176278444 cites W2113038626 @default.
- W2176278444 cites W2113318204 @default.
- W2176278444 cites W2114563488 @default.
- W2176278444 cites W2119423436 @default.
- W2176278444 cites W2123312213 @default.
- W2176278444 cites W2124880998 @default.
- W2176278444 cites W2146203649 @default.
- W2176278444 cites W2151144721 @default.
- W2176278444 cites W2585732487 @default.
- W2176278444 cites W4246616357 @default.
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- W2176278444 doi "https://doi.org/10.1111/jth.13208" @default.
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