The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin
Authors
Claytor, R. BrannonMichelson, Alan D.
Li, Jian-Ming
Frelinger, Andrew L. III
Rohrer, Michael J.
Garnette, Charles S. C.
Barnard, Marc R.
Krueger, Lori A.
Furman, Mark I.
Document Type
Journal ArticlePublication Date
2003-02-04Keywords
Cell AdhesionCell Division
Endothelium
Hemostatics
Humans
Peptide Fragments
Platelet Adhesiveness
Receptor, PAR-1
Receptors, Thrombin
Saphenous Vein
Thrombin
Venous Thrombosis
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
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.Source
J Vasc Surg. 2003 Feb;37(2):440-5. doi 10.1067/mva.2003.129DOI
10.1067/mva.2003.129Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43367PubMed ID
12563219Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1067/mva.2003.129