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The lectin compleme...
The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
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- Kozarcanin, Huda (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi
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- Lood, Christian (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital;Lund University
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- Munthe-Fog, L. (author)
- University of Copenhagen, Denmark
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- Sandholm, Kerstin (author)
- Linnaeus University,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC
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- Hamad, Osama A (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi
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- Bengtsson, Anders (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital;Lund University
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- Skjoedt, M. -O (author)
- University of Copenhagen, Denmark
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- Huber-Lang, M. (author)
- University Hospital of Ulm, Germany
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- Garred, P. (author)
- University of Copenhagen, Denmark
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- Nilsson Ekdahl, Kristina (author)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi
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- Nilsson, Bo (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:3, s. 531-545
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http://www.ncbi.nlm....
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Abstract
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- 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 invitro and invivo. 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 invitro. 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 invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- blood coagulation
- complement pathway
- mannose-binding lectin
- fibrin
- mannose-binding protein-associated serine proteases
- platelet activation
- Biomedical Sciences
- Biomedicinsk vetenskap
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kozarcanin, Huda
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Lood, Christian
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Munthe-Fog, L.
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Sandholm, Kersti ...
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Hamad, Osama A
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Bengtsson, Ander ...
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show more...
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Skjoedt, M. -O
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Huber-Lang, M.
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Garred, P.
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Nilsson Ekdahl, ...
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Nilsson, Bo
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Journal of Throm ...
- By the university
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Linnaeus University
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Lund University
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Uppsala University