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

Molecular Immunology
Lorenz JennyVerena Schroeder

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...Continue Reading

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Citations

Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·E M Conway
Dec 10, 2015·PloS One·Lorenz JennyVerena Schroeder
Oct 27, 2016·Immunological Reviews·Peter GarredMikkel-Ole Skjoedt
Jun 1, 2017·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Łukasz EppaMaciej Cedzyński
Mar 9, 2018·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Edward M Conway
Nov 5, 2016·Stroke; a Journal of Cerebral Circulation·Stefano Fumagalli, Maria-Grazia De Simoni
Jan 24, 2019·American Journal of Reproductive Immunology : AJRI·Julie Brogaard LarsenAnette Tarp Hansen
Jun 21, 2019·Journal of Thrombosis and Haemostasis : JTH·Robin A LiangJohn-Bjarne Hansen
May 28, 2019·Frontiers in Immunology·Márta L DebreczeniLászló Cervenak
Jul 24, 2020·Current Opinion in Hematology·Selin Oncul, Vahid Afshar-Kharghan
Aug 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paolo DuriguttoFrancesco Tedesco
Aug 6, 2020·International Journal of Molecular Sciences·Gabriela GajekMaciej Cedzyński
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Sep 4, 2020·British Journal of Pharmacology·Markus S Huber-LangChristian Karl Braun
Oct 16, 2021·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Komal ChoudharyKrishnan Hajela

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