Cargando…
Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII
Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with t...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331558/ https://www.ncbi.nlm.nih.gov/pubmed/25688860 http://dx.doi.org/10.1371/journal.pone.0116665 |
_version_ | 1782357741972488192 |
---|---|
author | Zakharova, Natalia V. Artemenko, Elena O. Podoplelova, Nadezhda A. Sveshnikova, Anastasia N. Demina, Irina A. Ataullakhanov, Fazly I. Panteleev, Mikhail A. |
author_facet | Zakharova, Natalia V. Artemenko, Elena O. Podoplelova, Nadezhda A. Sveshnikova, Anastasia N. Demina, Irina A. Ataullakhanov, Fazly I. Panteleev, Mikhail A. |
author_sort | Zakharova, Natalia V. |
collection | PubMed |
description | Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (k (i)/k (a) = 180 molecules/platelet). Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa), particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis. |
format | Online Article Text |
id | pubmed-4331558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43315582015-02-24 Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII Zakharova, Natalia V. Artemenko, Elena O. Podoplelova, Nadezhda A. Sveshnikova, Anastasia N. Demina, Irina A. Ataullakhanov, Fazly I. Panteleev, Mikhail A. PLoS One Research Article Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (k (i)/k (a) = 180 molecules/platelet). Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa), particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis. Public Library of Science 2015-02-17 /pmc/articles/PMC4331558/ /pubmed/25688860 http://dx.doi.org/10.1371/journal.pone.0116665 Text en © 2015 Zakharova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zakharova, Natalia V. Artemenko, Elena O. Podoplelova, Nadezhda A. Sveshnikova, Anastasia N. Demina, Irina A. Ataullakhanov, Fazly I. Panteleev, Mikhail A. Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title | Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title_full | Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title_fullStr | Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title_full_unstemmed | Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title_short | Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII |
title_sort | platelet surface-associated activation and secretion-mediated inhibition of coagulation factor xii |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331558/ https://www.ncbi.nlm.nih.gov/pubmed/25688860 http://dx.doi.org/10.1371/journal.pone.0116665 |
work_keys_str_mv | AT zakharovanataliav plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT artemenkoelenao plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT podoplelovanadezhdaa plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT sveshnikovaanastasian plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT deminairinaa plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT ataullakhanovfazlyi plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii AT panteleevmikhaila plateletsurfaceassociatedactivationandsecretionmediatedinhibitionofcoagulationfactorxii |