The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin
Department of Pediatrics; Department of Surgery
Cell Adhesion; Cell Division; Endothelium; Hemostatics; Humans; Peptide Fragments; Platelet Adhesiveness; Receptor, PAR-1; Receptors, Thrombin; Saphenous Vein; Thrombin; Venous Thrombosis
Hematology | Oncology | Pediatrics
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.
DOI of Published Version
J Vasc Surg. 2003 Feb;37(2):440-5. doi 10.1067/mva.2003.129
Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
Claytor R, Michelson AD, Li J, Frelinger AL, Rohrer MJ, Garnette CS, Barnard MR, Krueger LA, Furman MI. (2003). The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin. Hematology/Oncology. https://doi.org/10.1067/mva.2003.129. Retrieved from https://escholarship.umassmed.edu/peds_hematology/44