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Sökning: id:"swepub:oai:DiVA.org:lnu-52120" > The lectin compleme...

  • 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 ...

  • Elsevier BV,2016
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:lnu-52120
  • https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-52120URI
  • https://doi.org/10.1111/jth.13208DOI
  • https://lup.lub.lu.se/record/8234312URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279419URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 ...)

  • 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)
  • Munthe-Fog, L.University of Copenhagen, Denmark (författare)
  • Sandholm, KerstinLinnaeus University,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC(Swepub:lnu)jsake (författare)
  • Hamad, Osama AUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)osaha535 (författare)
  • 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)
  • Skjoedt, M. -OUniversity of Copenhagen, Denmark (författare)
  • Huber-Lang, M.University Hospital of Ulm, Germany (författare)
  • Garred, P.University of Copenhagen, Denmark (författare)
  • Nilsson Ekdahl, KristinaUppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi(Swepub:uu)krisnil (författare)
  • Nilsson, BoUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)bonils (författare)
  • Uppsala UniversityKlinisk immunologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Thrombosis and Haemostasis: Elsevier BV14:3, s. 531-5451538-79331538-7836

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