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Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1
Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499330/ https://www.ncbi.nlm.nih.gov/pubmed/36142125 http://dx.doi.org/10.3390/ijms231810203 |
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author | De Simone, Ilaria Baaten, Constance C. F. M. J. Jandrot-Perrus, Martine Gibbins, Jonathan M. ten Cate, Hugo Heemskerk, Johan W. M. Jones, Chris I. van der Meijden, Paola E. J. |
author_facet | De Simone, Ilaria Baaten, Constance C. F. M. J. Jandrot-Perrus, Martine Gibbins, Jonathan M. ten Cate, Hugo Heemskerk, Johan W. M. Jones, Chris I. van der Meijden, Paola E. J. |
author_sort | De Simone, Ilaria |
collection | PubMed |
description | Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the ‘supernatant of (hirudin-treated) coagulated plasma’ (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin α(IIb)β(3) activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by molecular blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors. |
format | Online Article Text |
id | pubmed-9499330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94993302022-09-23 Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 De Simone, Ilaria Baaten, Constance C. F. M. J. Jandrot-Perrus, Martine Gibbins, Jonathan M. ten Cate, Hugo Heemskerk, Johan W. M. Jones, Chris I. van der Meijden, Paola E. J. Int J Mol Sci Article Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the ‘supernatant of (hirudin-treated) coagulated plasma’ (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin α(IIb)β(3) activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by molecular blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors. MDPI 2022-09-06 /pmc/articles/PMC9499330/ /pubmed/36142125 http://dx.doi.org/10.3390/ijms231810203 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Simone, Ilaria Baaten, Constance C. F. M. J. Jandrot-Perrus, Martine Gibbins, Jonathan M. ten Cate, Hugo Heemskerk, Johan W. M. Jones, Chris I. van der Meijden, Paola E. J. Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title | Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title_full | Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title_fullStr | Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title_full_unstemmed | Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title_short | Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1 |
title_sort | coagulation factor xiiia and activated protein c activate platelets via gpvi and par1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499330/ https://www.ncbi.nlm.nih.gov/pubmed/36142125 http://dx.doi.org/10.3390/ijms231810203 |
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