Platelet adhesion receptors and (patho)physiological thrombus formation.
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 noncellular 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, alphaIIbbeta3 (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.
Andrews
R K
RK
Hanzel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Melbourne, Australia. rkandrews@hotmail.com
Shen
Y
Y
Gardiner
E E
EE
Berndt
M C
MC
D001792:Blood Platelets / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D005174:Factor XII / Q000502:physiology; D006801:Humans; D007704:Kininogens / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D008954:Models, Biological; D019007:P-Selectin / Q000502:physiology; D010973:Platelet Adhesiveness / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology; D015398:Signal Transduction; D013917:Thrombin / Q000502:physiology; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D014841:von Willebrand Factor / Q000502:physiology
D015815:Cell Adhesion Molecules; D007704:Kininogens; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D011961:Receptors, Fc; D014841:von Willebrand Factor; D005174:Factor XII; D013917:Thrombin