| Interaction of C1 inhibitor with thrombin on the endothelial surface. | |
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MedLine Citation:
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PMID: 21959589 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Thrombin, the central bioregulatory enzyme of haemostasis, also has a potent vasopermeability effect on the surface of endothelial cells, and has therefore been considered a major link between the activation of the coagulation pathway and inflammation. C1 inhibitor inhibits thrombin with a low second-order rate constant that can be increased by heparin. The aim of this study was to investigate whether the C1 inhibitor-induced inhibition of thrombin is potentiated on the endothelial surface. The interaction of C1 inhibitor and thrombin was evaluated in an in-vitro system of human umbilical vein endothelial cells (HUVECs) to which purified C1 inhibitor and thrombin have been added. The role of heparins and selectins has been tested by adding heparinase and Mab to selectins. Kinetic analysis under pseudo-first-order conditions showed that the inhibitory effect of C1 inhibitor on thrombin is greater on the surface of endothelial cells. After incubating nanomolar concentrations of thrombin and micromolar concentrations of C1 inhibitor in a purified system, thrombin activity remained significant, but was almost totally suppressed in the presence of HUVECs. The abolition of such suppression by heparinase and Mab to selectins supports the involvement of heparin and selectins in C1 inhibitor-thrombin interaction. Furthermore, the second-order rate constant was 25 ± 3 /s per mol/l in our purified system, but increased to 100 ± 9 /s per mol/l in the presence of HUVECs. Our results indicate that C1 inhibitor can inhibit thrombin activity on vascular endothelium via binding to selectins and potentiation by heparins. This may contribute to the modulation of thrombin activity on vasopermeability and on coagulation especially when the major natural anticoagulant pathways are impaired. |
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Authors:
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Sonia Caccia; Roberto Castelli; Diana Maiocchi; Luigi Bergamaschini; Massimo Cugno |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis Volume: 22 ISSN: 1473-5733 ISO Abbreviation: Blood Coagul. Fibrinolysis Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9102551 Medline TA: Blood Coagul Fibrinolysis Country: England |
Other Details:
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Languages: eng Pagination: 571-5 Citation Subset: IM |
Affiliation:
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aDepartment of Internal Medicine, IRCCS Foundation Ospedale Maggiore Policlinico, University of Milan bDepartment of Biomedical Sciences and Technologies, University of Milan, Milan, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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