Platelet integrins and immunoreceptors

Stable platelet adhesion to extracellular matrices and the formation of a hemostatic or pathological thrombus are dependent on integrin alpha IIb beta 3, also known as GPIIb-IIIa. However, maximal platelet responses to vascular injury may involve the participation of other integrins expressed in platelets (alpha V beta 3, alpha 2 beta 1, alpha 5 beta 1, and alpha 6 beta 1). Platelet membrane 'immunoreceptors' contain at least one subunit with an extracellular immunoglobulin superfamily domain and/or an intracellular stimulatory immunoreceptor tyrosine-based activation motif (ITAM) or immunoreceptor tyrosine-based inhibitory motif (ITIM). Platelet ITAM receptors, such as Fc gamma RIIA and the GPVI-FcR gamma complex, promote activation of integrins, while ITIM receptors, such as platelet-endothelial cell adhesion molecule-1, may promote their inhibition. This review summarizes the structure and function of platelet integrins and immunoreceptors, the emerging functional relationships between these receptor classes, and the consequences of their interaction for platelet function in hemostasis and thrombosis.