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The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2016 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 14, no 3, 531-545 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 14, no 3, 531-545 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-279419DOI: 10.1111/jth.13208ISI: 000372525100015OAI: oai:DiVA.org:uu-279419DiVA: diva2:908043
Funder
Swedish Research Council, 2013-65X-05647-34-4EU, FP7, Seventh Framework Programme, 602699
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2017-11-30Bibliographically approved

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Kozarcanin, HudaEkdahl, Kristina NNilsson, Bo

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