Adhesion and activation mechanisms supporting the hemostatic and prothrombotic function of platelets. Major ligands and receptors mediating platelet adhesion and activation at sites of vascular injury. Platelets are captured in the injured vessel wall from flowing blood through the specific interaction of the platelet GpIbIXV complex with collagenbound VWF exposed on the subendothelium (top). This ligandreceptor interaction has a rapid onoff rate that supports platelet translocation at the vessel wall. Stable platelet adhesion occurs through the binding of platelet GPVI to fibrillar collagen as well as ligation of collagen to 21. Once firmly adherent, platelets undergo a series of biochemical changes that induce integrin IIb3 activation, leading to the high affinity interaction with adhesion proteins including vWF, fibrinogen, and fibronectin. These adhesive interactions are indispensable for platelets to form stable aggregates with other activated platelets and promote thrombus growth. Activated platelets release or locally generate soluble agonists, including ADP, TXA2, and thrombin, that can induce autocrine or paracrine platelet activation (bottom). Each agonist activates specific G proteincoupled receptors on the platelet surface, including ADPP2Y1 or ADPP2Y12, TXA2TP, and thrombinPAR1 or PAR4, stimulating intracellular signaling events that include cytosolic calcium mobilization. This second messenger has a key role in promoting integrin IIb3 activation, TXA2 generation, granule secretion, and the procoagulant function of platelets. This figure also shows the point of antagonism of several FDAapproved antiplatelet drugs (abciximab, eptifibatide, tirofiban, clopidogrel, prasugrel, ticagrelor, and aspirin) and two experimental PAR1 inhibitors (SCH530348 and E5555). Abbreviations: GP glycoprotein, PAR protease activated receptor, P purinergic, ADP adenosine diphosphate, TXA thromboxane, TP TXA2 receptor, G heterotrimeric GTP binding protein, FcR Fc receptor gamma chain, ITAM immunoreceptor tyrosinebased activation motif, vWF von Willebrand factor, PLA2 phospholipase A2, COX cyclooxygenase, AA arachidonic acid, PGH2 prostaglandin H2, IP3R inositol1,4,5trisphosphate receptor, DTS dense tubular system. This figure was originally published in Nature Medicine by Nature Publishing Group. Arterial thrombosis insidious, unpredictable and deadly by Shaun P. Jackson in Nature Medicine 2011;11:14231436. Reproduced with permission of Nature Publishing Group in the format reuse in a journal via Copyright Clearance Center.
Additional keywords: adhesion,tethering,immunology,platelets,treatment