The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin
| Autor: | Marc R. Barnard, Lori A. Krueger, Charles S. C. Garnette, R.Brannon Claytor, Alan D. Michelson, Jian-ming Li, Andrew L. Frelinger, Michael J. Rohrer, Mark I. Furman |
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| Rok vydání: | 2003 |
| Předmět: |
In Vitro Techniques
Hemostatics chemistry.chemical_compound Platelet Adhesiveness Thrombin Cell–cell interaction Platelet adhesiveness Cell Adhesion medicine Humans Receptor PAR-1 Saphenous Vein Platelet Endothelium Platelet activation Cell adhesion Venous Thrombosis business.industry Molecular biology Peptide Fragments Endothelial stem cell Adenosine diphosphate chemistry Immunology Receptors Thrombin Surgery Cardiology and Cardiovascular Medicine business Cell Division medicine.drug |
| Zdroj: | Journal of Vascular Surgery. 37:440-445 |
| ISSN: | 0741-5214 |
| DOI: | 10.1067/mva.2003.129 |
| Popis: | Purpose: Platelet-endothelial cell adhesion is an important pathologic response to vessel injury or inflammation. On binding to its endothelial or platelet G protein-linked seven-transmembrane domain receptor, protease-activated receptor-1 (PAR1), thrombin releases a 41-amino acid peptide (TR 1-41 ). We examined the effect of TR 1-41 on platelet activation and on platelet-endothelial cell adhesion. Methods: A monolayer of confluent human saphenous vein endothelial cells was incubated with washed human platelets. Platelets were stimulated with either TR 1-41 , TR 21-41 , scrambled TR 1-41 , adenosine diphosphate (ADP)-epinephrine (EPI), thrombin, or thrombin receptor activating peptide (TRAP). Platelet activation was identified with flow cytometry. The magnitude of platelet-endothelial cell adhesion was determined with a laser scanning cytometer that scanned the monolayer of endothelial cells and identified fluorescently bound platelets. Results: Maximal thrombin stimulation (0.1 U/mL) induced a threefold increase in platelets bound to endothelial cells compared with buffer alone. Stimulation with TR 1-41 (20 mmol/L) tripled the number of platelets bound to endothelial cells compared with thrombin. Scrambled sequence of TR 1-41 (20 mmol/L) and TR 21-41 (20 mmol/L), neither of which induces platelet activation, had minimal effect on platelet adhesion. Both TRAP (20 mmol/L) and ADP-EPI (20 mmol/L) induced less platelet-endothelial cell adhesion than did thrombin. TR 1-41 -induced platelet-endothelial cell adhesion was partially blocked by glycoprotein (GP)IIb-IIIa-specific monoclonal antibody, 10E5 (10 mg/mL). Conclusions: TR 1-41 , the cleaved peptide of PAR1, is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin, TRAP, or ADP-EPI, and this adhesion is at least in part mediated by the platelet GPIIb-IIIa receptor. (J Vasc Surg 2003;37:440-5.) |
| Databáze: | OpenAIRE |
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