Beyond Clotting: A Role of Platelets in CNS Repair?

Platelets are small, oval, circulating, anucleate cells that upon endothelial damage form a haemostatic plug and stop blood leakage. Circulating platelets derive from bone-marrow-resident megakaryocytes that daily produce and release approximately 100 billions of new platelets into the blood stream (Kaushansky, 2006; Semple et al., 2011). During haemostasis, tethering platelets adhere to the vascular injury through the interaction between their glycoprotein (GP) Ib/V/IX receptor complex and GP VI/GP Ia with the von Willebrand factor (vWF) and collagen provided by the lesioned environment, respectively. Adherent platelets aggregate and secrete platelet activation mediators, such as Thromboxane A2 (TXA2) and adenosine diphosphate (ADP). After activation, the platelets membrane surface becomes procoagulant enhancing the coagulation cascade ending in the formation and stabilization of the haemostatic plug and arresting blood leakage. Platelet function is not restricted to haemostasis, as platelets also have inflammatory, angiogenic, and tissue repair properties (Nurden, 2011). Within their storage compartments (α-granules and dense granules), platelets store a plethora of bioactive molecules that, under specific circumstances, are secreted to the extracellular space targeting other cell types. Platelets-derived molecules include proteins such as chemokines, cytokines, and growth factors, as well as RNAs and microparticles Warnke et al., 2013). Platelets granules contain several pro-inflammatory and anti-inflammatory molecules that contribute to immunity. In fact, platelets react against pathogens and regulate immune cells function (reviewed in Semple et al., 2011). For example, during inflammation, GPIbα, and P-selectin located at the surface of platelets interact with PSGL-1 and Mac-1 on monocytes/macrophages inducing their recruitment and activation (reviwed in Gawaz et al., 2005). Also, CD154 in activated platelets (Henn et al., 1998) binds to CD40 on endothelial cells (ECs) inducing the expression of cell adhesion molecules (i.e., VCAM1, ICAM1) and the endothelial release of CC-chemokine ligand 2 (CCL2) promoting the leukocyte recruitment to inflammatory sites (Andre et al., 2002). Moreover, CD154 supports B cell differentiation (Elzey et al., 2003; Von Hundelshausen and Weber, 2007) and platelet-secreted transforming growth factor beta (TGF-β) controls T reg cell differentiation (Tran, 2012) indicating that the contribution of platelets to immunity is not restricted to the innate system but also involves adaptive response. Platelets apparently also shape angiogenesis, which is a complex process that consists in the formation/sprouting of new capillaries from preexisting vessels. Platelets have a dual role.