Platelet adhesion receptors and (patho)physiological thrombus formation

R.K. Andrews, Y. Shen, E.E. Gardiner and M.C. Berndt

Hanzel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Melbourne, Australia

Offprint requests to: Dr. Robert K. Andrews, Baker Medical Research Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Australia 8008. Fax: 61-3-9521-1362. e-mail: rkandrews@hotmail.com

Summary. In thrombus formation associated with hemostasis or thrombotic disease, blood platelets first undergo a rapid transition from a circulating state to an adherent state, followed by activation and aggregation. Under flow conditions in the bloodstream, this process potentially involves platelet-platelet, platelet-endothelium, platelet-subendothelial matrix, and platelet-leukocyte interactions. Specific adhesion receptors on platelets mediate these interactions, by engaging counter-receptors on other cells, or non-cellular ligands in the plasma or matrix. The glycoprotein (GP) Ib-IX-V complex on platelets initiates adhesion at high shear stress by binding the adhesive ligand, von Willebrand Factor (vWF). GP Ib-IX-V may also mediate platelet-endothelium or platelet-leukocyte adhesion, by recognition of P-selectin or Mac-1, respectively. Other membrane glycoproteins, such as the collagen receptor GP VI, may trigger platelet activation at low shear rates. Engagement of GP Ib-IX-V or GP VI leads ultimately to platelet aggregation mediated by the integrin, aIIbß3 (GP IIb-IIIa). This review will focus on recent advances in understanding structure-activity relationships of GP Ib-IX-V, its role in initiating thrombus formation, and its emerging relationships with other vascular cell adhesion receptors. Histol. Histopathol. 16, 969-980 (2001)

Key words: Glycoprotein Ib-IX-V, Platelets, Thrombosis, von Willebrand Factor

DOI: 10.14670/HH-16.969