Platelet apoptosis by cold‐induced glycoprotein Ibα clustering

Abstract

To cite this article: van der Wal DE, Du VX, Lo KSL, Rasmussen JT, Verhoef S, Akkerman JWN. Platelet apoptosis by cold-induced glycoprotein Iba clustering. J Thromb Haemost 2010; 8: 2554-62.Summary. Background: Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Iba-distribution indicative of receptor clustering and initiates thromboxane A 2 -formation. GPIba is associated with 14-3-3 proteins, which contribute to GPIba-signaling and in nucleated cells take part in apoptosis regulation. Objectives and methods: We investigated whether GPIba-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0°C)-rewarming (1 h 37°C). Results: During cold-rewarming, 14-3-3 proteins associate with GPIba and dissociate from Bad inducing Baddephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-x L and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-D-glucosamine (GN), which blocks GPIba-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIba. Conclusions: Cold-rewarming triggers apoptosis through a GN-sensitive GPIba-change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIba-change.

Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ib - 14-3-3 ] association

“…2,21 Figure 1A confirms these observations for the ΔΨ m change and shows a 7-fold increase after incubation for 4 h at 0°C. Cold/rewarming initiates formation of TxA 2 .…”

“…We showed earlier that the ΔΨ m change in cold-stored platelets is accompanied by a fall in [14-3-3ζ-Bad]. 2 To investigate whether AA contributes to this process, platelets with blocked TPα were incubated at 0°C (4 h) and subsequently incubated at 37°C (1 h) and the complex was measured in immunoprecipitates of Bad. Cold/rewarming induced a fall in [14-3-3ζ-Bad] ( Figure 3A).…”

“…Improvements are sought by cooling the concentrates to 0-4°C, but this introduces new problems as it induces redistribution of the von Willebrand factor (VWF) receptor, glycoprotein (GP) Ibα. The change in GPIbα starts apoptosis, 2 platelet destruction by macrophages 3 and generation of thromboxane A 2 (TxA 2 ) upon rewarming. 4 We previously described that the cold-induced change makes GPIbα a "sink" for the adapter protein 14-3-3ζ.…”

“…4 We previously described that the cold-induced change makes GPIbα a "sink" for the adapter protein 14-3-3ζ. 2 Formation of a [14-3-3ζ-GPIbα] complex is accompanied by dissociation of [14-3-3ζ-phosphoBad], inducing Bad activation, a fall in mitochondrial membrane potential (ΔΨ m ) and caspase-9 activation. These reactions drive the surface exposure of phosphatidylserine (PS) which together with GPIbα and surface-expressed P-selectin mediate binding to macrophages and platelet destruction.…”

Dietary α-linolenic acid increases the platelet count in ApoE−/− mice by reducing clearance

“…[1][2][3][4][5][6] Long-chain omega-3 fatty acids (LCn3-FAs) exert beneficial cardiovascular effects on atherosclerosis and inflammation and have been demonstrated to induce antithrombotic and antiplatelet effects and to reduce mortality. [7][8][9][10][11][12][13] Although the Alpha Omega Trial did not show a significantly different event rate among patients receiving LCn3-FA in addition to state-of-the-art therapy for myocardial infarction, 14 previous studies and subgroup analyses demonstrated a beneficial effect of omega (v)-3 FA.…”