Protease: Serpin complexes to assess contact system and intrinsic pathway activation
Abstract Mounting evidence suggests that a variety of disease states are pathophysiologically related to activation of the contact system in vivo. The plasma contact system is composed of a cascade of serine proteases initiated by surface activation of factor XII, which can then proceed through a pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12389 |
| _version_ | 1827887081267920896 |
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| author | Michael W. Henderson Denis F. Noubouossie Anton Ilich Kathy J. Wilson Rafal Pawlinski Dougald M. Monroe Nigel S. Key |
| author_facet | Michael W. Henderson Denis F. Noubouossie Anton Ilich Kathy J. Wilson Rafal Pawlinski Dougald M. Monroe Nigel S. Key |
| author_sort | Michael W. Henderson |
| collection | DOAJ |
| description | Abstract Mounting evidence suggests that a variety of disease states are pathophysiologically related to activation of the contact system in vivo. The plasma contact system is composed of a cascade of serine proteases initiated by surface activation of factor XII, which can then proceed through a procoagulant pathway by activating the intrinsic coagulation factor XI, or a proinflammatory pathway by activating prekallikrein. Serpins are the primary endogenous inhibitors of the contact system, which irreversibly inhibit their respective protease(s), forming a stable complex. We modified an existing assay strategy for detecting these complexes in plasma using ELISAs and determined the effect of preanalytical variation caused by anticoagulant selection and processing time. The assays were sensitive and specific to inherited deficiency of individual contact factors. We conclude that these assays are robust and represent a relatively simple approach to the assessment of contact factor activation in plasma samples. |
| first_indexed | 2024-03-12T20:13:07Z |
| format | Article |
| id | doaj.art-ef9e3503ced04bb0a1cc394be1c50aa8 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T20:13:07Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-ef9e3503ced04bb0a1cc394be1c50aa82023-08-02T01:35:42ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792020-07-014578979810.1002/rth2.12389Protease: Serpin complexes to assess contact system and intrinsic pathway activationMichael W. Henderson0Denis F. Noubouossie1Anton Ilich2Kathy J. Wilson3Rafal Pawlinski4Dougald M. Monroe5Nigel S. Key6Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill Chapel Hill NC USAUNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USAUNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USAUNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USAUNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USAUNC Blood Research Center University of North Carolina at Chapel Hill Chapel Hill NC USADepartment of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill Chapel Hill NC USAAbstract Mounting evidence suggests that a variety of disease states are pathophysiologically related to activation of the contact system in vivo. The plasma contact system is composed of a cascade of serine proteases initiated by surface activation of factor XII, which can then proceed through a procoagulant pathway by activating the intrinsic coagulation factor XI, or a proinflammatory pathway by activating prekallikrein. Serpins are the primary endogenous inhibitors of the contact system, which irreversibly inhibit their respective protease(s), forming a stable complex. We modified an existing assay strategy for detecting these complexes in plasma using ELISAs and determined the effect of preanalytical variation caused by anticoagulant selection and processing time. The assays were sensitive and specific to inherited deficiency of individual contact factors. We conclude that these assays are robust and represent a relatively simple approach to the assessment of contact factor activation in plasma samples.https://doi.org/10.1002/rth2.12389anticoagulantenzymefactor XIfactor XIIkallikreinserpin |
| spellingShingle | Michael W. Henderson Denis F. Noubouossie Anton Ilich Kathy J. Wilson Rafal Pawlinski Dougald M. Monroe Nigel S. Key Protease: Serpin complexes to assess contact system and intrinsic pathway activation Research and Practice in Thrombosis and Haemostasis anticoagulant enzyme factor XI factor XII kallikrein serpin |
| title | Protease: Serpin complexes to assess contact system and intrinsic pathway activation |
| title_full | Protease: Serpin complexes to assess contact system and intrinsic pathway activation |
| title_fullStr | Protease: Serpin complexes to assess contact system and intrinsic pathway activation |
| title_full_unstemmed | Protease: Serpin complexes to assess contact system and intrinsic pathway activation |
| title_short | Protease: Serpin complexes to assess contact system and intrinsic pathway activation |
| title_sort | protease serpin complexes to assess contact system and intrinsic pathway activation |
| topic | anticoagulant enzyme factor XI factor XII kallikrein serpin |
| url | https://doi.org/10.1002/rth2.12389 |
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