Platelet immunology: Structure, functions, and polymorphisms of membrane glycoproteins

INTRODUCTION The main function of platelets is to arrest bleeding by forming a hemostatic plug through their interaction with damaged vascular wall. It is well recognized that platelets also play a crucial role in the formation of pathologic thrombus to occlude vasculature, leading to fatal diseases such as acute coronary syndrome or stroke. In addition, platelets are involved in various physiologic or pathologic processes such as inflammation, antimicrobial host defense, immune regulation, tumor growth, and metastasis. Platelets express many types of receptors on their surface to interact with a wide variety of stimuli and adhesive proteins. Because platelets play a major role in hemostasis, the molecular mechanisms of hemostatic thrombus formation have been extensively studied. Platelets first interact with exposed subendothelial matrix protein, collagen, in damaged vascular wall. Circulating platelets then form a large aggregate over the layer of platelets adhered to vascular wall, together with fibrin formation to complete the hemostatic process. Like many other cells, platelets express integrin receptors involved in adhesive and signaling processes. Integrins consist of noncovalently linked heterodimers of α and β subunits. They are usually present on the cell surface in a low- or high-affinity state. Transition between these two states is regulated by cytoplasmic signals generated when cells are stimulated or activated. Platelets exhibit six integrins: α2β1, α5β1, α6β1, αLβ2, αIIbβ3, and αvβ3.