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 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.
Plenchette
S
S
INSERM U517, Faculty of Medicine, Dijon, France.
Moutet
M
M
Benguella
M
M
N'Gondara
J P
JP
Guigner
F
F
Coffe
C
C
Corcos
L
L
Bettaieb
A
A
Solary
E
E
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D001793:Blood Preservation; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism; D017713:Platelet Transfusion; D011498:Protein Precursors / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D013048:Specimen Handling; D013997:Time Factors; D053319:Tumor Necrosis Factor Decoy Receptors
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D020169:Caspases; D004121:Dimethyl Sulfoxide