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

Jenny, Lorenz; Dobó, József; Gál, Péter; Schroeder, Verena (2015). MASP-1 of the complement system promotes clotting via prothrombin activation. Molecular immunology, 65(2), pp. 398-405. Elsevier 10.1016/j.molimm.2015.02.014

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Experimentelle Hämostase
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Thromboselabor Kinderklinik [discontinued]

UniBE Contributor:

Jenny, Lorenz and Schröder, Verena

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0161-5890

Publisher:

Elsevier

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

29 Apr 2015 12:12

Last Modified:

10 Dec 2019 14:42

Publisher DOI:

10.1016/j.molimm.2015.02.014

PubMed ID:

25745807

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.67427

URI:

https://boris.unibe.ch/id/eprint/67427

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