Shedding New Light on the Platelet Storage Lesion

In this issue of ATVB , Chen et al1 report that a monoclonal antibody whose epitope includes the ADAM17 cleavage site in human platelet glycoprotein Ibα (GPIbα) inhibits GPIbα shedding during platelet storage under blood banking conditions and improves the recovery and survival of platelets in murine platelet transfusion models.See accompanying article on page 1821 The lifespan of circulating endogenous platelets is determined by a combination of random platelet removal and a nonrandom aging mechanism after which senescent platelets are removed by the reticuloendothelial system. At least a portion of platelet senescence is regulated by an intrinsic apoptotic pathway that acts as an internal timer.2,3 Platelets contain members of the antiapoptotic Bcl-2 family, such as Bcl-xL, as well as the proapoptotic proteins Bax and Bak.2,4 The half-life of Bcl-xL in platelets is shorter than that of Bak.2,5 Thus, it is likely that as the effect of Bcl-xL declines, a point is reached at which Bak is able to cause platelet apoptosis.3 How apoptosis causes platelet clearance is unknown. Apoptosis causes phosphotidylserine exposure on cell surfaces, a signal for the phagocytosis of apoptotic cells,6 but it remains to be …