Glycoprotein Ibα–Mediated Platelet Adhesion and Aggregation to Immobilized Thrombin Under Conditions of Flow

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 26; no. 3; pp. 670 - 675
• Main Authors: Weeterings, Cees, Adelmeijer, Jelle, Myles, Timothy, de Groot, Philip G, Lisman, Ton
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.03.2006; Hagerstown, MD Lippincott
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood vessels and receptors; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Medical sciences; Molecular and cellular biology; Platelet; Vertebrates: cardiovascular system; GPIbα; Serine endopeptidases; Hemostatic; Enzyme; Glycoprotein; Cardiovascular disease; Thrombin; Vascular disease; Aggregation; Peptidases; Fibrin; flow conditions; Platelet; Atherosclerosis; Hydrolases
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000200391.70818.a9

OBJECTIVES—Thrombin interacts with platelets via the protease-activated receptors (PARs) 1 and 4, and via glycoprotein Ibα (GPIbα). Recently, it was shown that platelets are able to adhere to immobilized thrombin under static conditions via GPIbα. METHODS AND RESULTS—Here, we show that platelets are also able to adhere to and form stable aggregates on immobilized thrombin under conditions of flow. Adhesion and aggregation to thrombin was dependent on the interaction with GPIbα, as addition of glycocalicin or an antibody blocking the interaction between thrombin and GPIbα inhibited platelet adhesion. Additionally, platelet adhesion to recombinant thrombin mutants, which are unable to bind GPIbα, was severely suppressed. Furthermore, platelet adhesion to thrombin was dependent on activation of PARs, and partly on granule secretion and thromboxane-A2 synthesis. Immobilization of thrombin on a fibrin network resulted in substantially increased adhesion compared with fibrin alone. The adhesion to fibrin alone was completely abolished by addition of dRGDW, whereas fibrin-bound thrombin still showed substantial platelet adhesion in the presence of dRGDW, indicating that fibrin-bound thrombin is able to directly capture platelets under flow. CONCLUSION—These results indicate that platelets are able to adhere to thrombin under flow conditions, which is dependent on the interaction with GPIbα.