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

Leukemia volume 15, pages 1572–1581 (2001)Cite this article

Abstract

Platelet transfusion is widely used to prevent bleeding in patients with severe thrombocytopenia. The maximal storage duration of platelet concentrates is usually 5 days, due to the platelet storage lesion that impairs their functions when stored for longer times. Some of the morphological and biochemical changes that characterize this storage lesion are reminiscent of cell death by apoptosis. The present study analyzed whether proteins involved in nucleated cell apoptosis could play a role in the platelet storage lesion. Storage of leukocyte-depleted platelets obtained by apheresis is associated 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 the pro-apoptotic mitochondrial protein Diablo/Smac in the cytosol. Platelets do not express the death receptors Fas, DR4 and DR5 on their plasma membrane, while the expression of the decoy receptor DcR2 increases progressively during platelet storage. Addition of low concentrations of the cryoprotector dimethylsulfoxide accelerates platelet caspase activation during storage, an effect that is partially prevented by the caspase inhibitor z-VAD-fmk. Altogether, DcR2 expression on the plasma membrane is an early event while caspase activation is a late event during platelet storage. These observations suggest that caspases are unlikely to account for the platelet storage lesion. As a consequence, addition of caspase inhibitors may not improve the quality of platelet concentrates stored in standard conditions.

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Acknowledgements

This work was supported by a grant from the Association pour la Recherche en Transfusion. The group is also labeled ‘La Ligue’ by the Ligue Nationale Contre le Cancer. We thank Dr Jean-Pierre Cazenave (INSERM U311, Strasbourg, France) for helpful advices during the course of the study and Dr Kubin, Dr Yagita and Dr Wang for providing Abs.

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Authors and Affiliations

  1. INSERM U517, Dijon, France

    S Plenchette, M Moutet, L Corcos, A Bettaieb & E Solary

  2. Etablissement Français du Sang de Bourgogne-Franche-Comté, Dijon, France

    M Benguella, JP N'Gondara, F Guigner & C Coffe

  3. Clinical Hematology Unit, CHU Le Bocage, Dijon, France

    E Solary

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Plenchette, S., Moutet, M., Benguella, M. et al. Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion. Leukemia 15, 1572–1581 (2001). https://doi.org/10.1038/sj.leu.2402231

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