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The lectin compleme...
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Kozarcanin, HudaUppsala universitet,Uppsala University,Klinisk immunologi
(författare)
The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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Elsevier BV,2016
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:lnu-52120
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https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-52120URI
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https://doi.org/10.1111/jth.13208DOI
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https://lup.lub.lu.se/record/8234312URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279419URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lood, ChristianLund 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(Swepub:lu)med-ctl
(författare)
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Munthe-Fog, L.University of Copenhagen, Denmark
(författare)
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Sandholm, KerstinLinnaeus University,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC(Swepub:lnu)jsake
(författare)
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Hamad, Osama AUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)osaha535
(författare)
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Bengtsson, AndersLund 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(Swepub:lu)reum-abe
(författare)
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Skjoedt, M. -OUniversity of Copenhagen, Denmark
(författare)
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Huber-Lang, M.University Hospital of Ulm, Germany
(författare)
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Garred, P.University of Copenhagen, Denmark
(författare)
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Nilsson Ekdahl, KristinaUppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi(Swepub:uu)krisnil
(författare)
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Nilsson, BoUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)bonils
(författare)
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Uppsala UniversityKlinisk immunologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Thrombosis and Haemostasis: Elsevier BV14:3, s. 531-5451538-79331538-7836
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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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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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