MASP-1 of the complement system promotes clotting via prothrombin activation

Lorenz Jenny, József Dobó, Péter Gál, Verena Schroeder

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Mannan-binding lectin-associated serine protease-1 (MASP-1), a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity, and it has been shown to activate coagulation factors. Here we studied the effects of MASP-1 on clot formation in whole blood (WB) and platelet-poor plasma (PPP) by thrombelastography and further elucidated the underlying mechanism. Cleavage of prothrombin by MASP-1 was investigated by SDS-PAGE and N-terminal sequencing of cleavage products. Addition of MASP-1 or thrombin to WB and PPP shortened the clotting time and clot formation time significantly compared to recalcified-only samples. The combination of MASP-1 and thrombin had additive effects. In a purified system, MASP-1 was able to induce clotting only in presence of prothrombin. Analysis of MASP-1-digested prothrombin confirmed that MASP-1 cleaves prothrombin at three cleavage sites. In conclusion, we have shown that MASP-1 is able to induce and promote clot formation measured in a global setting using the technique of thrombelastography. We further confirmed that MASP-1-induced clotting is dependent on prothrombin. Finally, we have demonstrated that MASP-1 cleaves prothrombin and identified its cleavage sites, suggesting that MASP-1 gives rise to an alternative active form of thrombin by cleaving at the cleavage site R393.

Original languageEnglish
Pages (from-to)398-405
Number of pages8
JournalMolecular Immunology
Volume65
Issue number2
DOIs
Publication statusPublished - Jun 1 2015

Keywords

  • Coagulation
  • Complement system
  • MASP-1
  • Mannan-binding lectin-associated serine protease
  • Prothrombin
  • Thrombelastography

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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