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

Jenny, Lorenz and Dobó, József and Gál, Péter and Schroeder, Verena (2015) MASP-1 of the complement system promotes clotting via prothrombin activation. MOLECULAR IMMUNOLOGY, 65 (2). pp. 398-405. ISSN 0161-5890

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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. © 2015 Elsevier Ltd.

Item Type: Article
Uncontrolled Keywords: thromboelastography; thrombocyte poor plasma; protein blood level; priority journal; polyacrylamide gel electrophoresis; human; fibrin formation; controlled study; blood clotting time; blood clotting; ARTICLE; amino terminal sequence; unclassified drug; THROMBIN; mannan binding lectin associated serine proteinase 1; mannan binding lectin associated serine proteinase; FIBRINOGEN; Thrombelastography; prothrombin; MASP-1; Mannan-binding lectin-associated serine protease; Complement system; COAGULATION
Subjects: Q Science / természettudomány > QR Microbiology / mikrobiológia > QR180 Immunology / immunológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 03 Jul 2015 08:17
Last Modified: 03 Jul 2015 08:17
URI: http://real.mtak.hu/id/eprint/25075

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