Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion

Platelet transfusion is widely used to prevent bleeding in patients with se vere thrombocytopenia. The maximal storage duration of platelet concentrate s is usually 5 days, due to the platelet storage lesion that impairs their functions when stored for longer times. Some of the morphological and bioch emical changes that characterize this storage lesion are reminiscent of cel l death by apoptosis. The present study analyzed whether proteins involved in nucleated cell apoptosis could play a role in the platelet storage lesio n. Storage of leukocyte-depleted platelets obtained by apheresis is associa ted with a late and limited activation of caspases, mainly caspase-3. This event correlates with an increased expression of the pro-apoptotic BH3-only protein Bim in the particulate fraction and a slight and late release of t he pro-apoptotic mitochondrial protein Diablo/Smac in the cytosol. Platelet s do not express the death receptors Fas, DR4 and DR5 on their plasma membr ane, while the expression of the decoy receptor DcR2 increases progressivel y during platelet storage. Addition of low concentrations of the cryoprotec tor dimethylsulfoxide accelerates platelet caspase activation during storag e, an effect that is partially prevented by the caspase inhibitor z-VAD-fmk . Altogether, DcR2 expression on the plasma membrane is an early event whil e caspase activation is a late event during platelet storage. These observa tions suggest that caspases are unlikely to account for the platelet storag e lesion. As a consequence, addition of caspase inhibitors may not improve the quality of platelet concentrates stored in standard conditions.