Effects of Thrombin on Interactions Between b3-Integrins and Extracellular Matrix in Platelets and Vascular Cells

The b3-integrin family consists of aIIbb3 (also known as glycoprotein IIb/IIIa) and avb3. aIIbb3 is found on platelets and megakaryocytes and has an essential role in hemostasis. avb3 has a broader distribution, and it functions in angiogenesis, neointimal formation after vascular injury, and leukocyte trafficking. There are important interactions between thrombin and b32integrins relative to both “inside-out” (integrin activation) and “outside-in” (modification of cellular events by ligand binding to integrins) signaling. Thrombin, by binding to G protein–coupled, protease-activated receptors, is a potent activator of aIIbb3. Conversely, outside-in signaling through aIIbb3 amplifies events initiated by thrombin and is necessary for full platelet spreading, platelet aggregation, granule secretion, and the formation of a stable platelet thrombus. In smooth muscle cells, avb3-integrins influence various responses to thrombin, including proliferation, c-Jun NH2-terminal kinase-1 activation, and focal adhesion formation. Other interactions between b3-integrins and thrombin include b3-integrin promotion of the generation of thrombin by localizing prothrombin to cellular surfaces and/or enhancing the formation of procoagulant microparticles and the requirement of b3-integrin function for platelet-dependent clot retraction. In summary, there is increasing evidence that interactions between b3-integrins and thrombin play important roles in the regulation of hemostatic and vascular functions. (Arterioscler Thromb Vasc Biol. 2003;23:●●●-●●●.)