Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation.
BACKGROUND: Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3335018?pdf=render |
| _version_ | 1828156993299283968 |
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| author | Katharina Hess Ramzi Ajjan Fladia Phoenix József Dobó Péter Gál Verena Schroeder |
| author_facet | Katharina Hess Ramzi Ajjan Fladia Phoenix József Dobó Péter Gál Verena Schroeder |
| author_sort | Katharina Hess |
| collection | DOAJ |
| description | BACKGROUND: Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of factor XIII (FXIII), fibrinogen, prothrombin, and thrombin-activatable fibrinolysis inhibitor (TAFI) in plasma-based systems, and to analyse effects of MASP-1 on plasma clot formation, structure and lysis. METHODOLOGY/PRINCIPAL FINDINGS: We used a FXIII incorporation assay and specific assays to measure the activation products prothrombin fragment F1+2, fibrinopeptide A (FPA), and activated TAFI (TAFIa). Clot formation and lysis were assessed by turbidimetric assay. Clot structure was studied by scanning electron microscopy. MASP-1 activated FXIII and, contrary to thrombin, induced FXIII activity faster in the Val34 than the Leu34 variant. MASP-1-dependent generation of F1+2, FPA and TAFIa showed a dose-dependent response in normal citrated plasma (NCP), albeit MASP-1 was much less efficient than FXa or thrombin. MASP-1 activation of prothrombin and TAFI cleavage were confirmed in purified systems. No FPA generation was observed in prothrombin-depleted plasma. MASP-1 induced clot formation in NCP, affected clot structure, and prolonged clot lysis. CONCLUSIONS/SIGNIFICANCE: We show that MASP-1 interacts with plasma clot formation on different levels and influences fibrin structure. Although MASP-1-induced fibrin formation is thrombin-dependent, MASP-1 directly activates prothrombin, FXIII and TAFI. We suggest that MASP-1, in concerted action with other complement and coagulation proteins, may play a role in fibrin clot formation. |
| first_indexed | 2024-04-11T23:22:09Z |
| format | Article |
| id | doaj.art-675ede2402c849af85cda6f39505971b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:22:09Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-675ede2402c849af85cda6f39505971b2022-12-22T03:57:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3569010.1371/journal.pone.0035690Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation.Katharina HessRamzi AjjanFladia PhoenixJózsef DobóPéter GálVerena SchroederBACKGROUND: Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of factor XIII (FXIII), fibrinogen, prothrombin, and thrombin-activatable fibrinolysis inhibitor (TAFI) in plasma-based systems, and to analyse effects of MASP-1 on plasma clot formation, structure and lysis. METHODOLOGY/PRINCIPAL FINDINGS: We used a FXIII incorporation assay and specific assays to measure the activation products prothrombin fragment F1+2, fibrinopeptide A (FPA), and activated TAFI (TAFIa). Clot formation and lysis were assessed by turbidimetric assay. Clot structure was studied by scanning electron microscopy. MASP-1 activated FXIII and, contrary to thrombin, induced FXIII activity faster in the Val34 than the Leu34 variant. MASP-1-dependent generation of F1+2, FPA and TAFIa showed a dose-dependent response in normal citrated plasma (NCP), albeit MASP-1 was much less efficient than FXa or thrombin. MASP-1 activation of prothrombin and TAFI cleavage were confirmed in purified systems. No FPA generation was observed in prothrombin-depleted plasma. MASP-1 induced clot formation in NCP, affected clot structure, and prolonged clot lysis. CONCLUSIONS/SIGNIFICANCE: We show that MASP-1 interacts with plasma clot formation on different levels and influences fibrin structure. Although MASP-1-induced fibrin formation is thrombin-dependent, MASP-1 directly activates prothrombin, FXIII and TAFI. We suggest that MASP-1, in concerted action with other complement and coagulation proteins, may play a role in fibrin clot formation.http://europepmc.org/articles/PMC3335018?pdf=render |
| spellingShingle | Katharina Hess Ramzi Ajjan Fladia Phoenix József Dobó Péter Gál Verena Schroeder Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PLoS ONE |
| title | Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. |
| title_full | Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. |
| title_fullStr | Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. |
| title_full_unstemmed | Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. |
| title_short | Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. |
| title_sort | effects of masp 1 of the complement system on activation of coagulation factors and plasma clot formation |
| url | http://europepmc.org/articles/PMC3335018?pdf=render |
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