Platelet activation and apoptosis are different phenomena: evidence from the sequential dynamics and the magnitude of responses during platelet storage

Leytin, Valery; Allen, David J.; Mutlu, Asuman; Mykhaylov, Sergiy; Lyubimov, Elena; Freedman, John

doi:10.1111/j.1365-2141.2008.07209.x

Cited by 57 publications

(63 citation statements)

References 11 publications

(14 reference statements)

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“…Others have also shown an increase in PS exposure during storage, but to various degrees [6,16,18,30], the consequences of these apoptotic features during storage are largely unknown. Our results are in accordance with the results by Leytin et al [32] that platelet activation is triggered before exposure of apoptotic features and our results support the hypothesis that apoptosis is triggered beyond the current shelf-life [1,30]. It was also after day 7 that greatest changes in platelet adhesion and activation response occurred and they coincided with an increased rate in glucose consumption-and lactate formation.…”

Section: Discussionsupporting

confidence: 93%

Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads

et al. 2014

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The aim of the present study was to set up and evaluate a novel method for studies of platelet adhesion and activation in blood and platelet suspensions such as platelet concentrate (PC) samples using protein-coated polystyrene beads and flow cytometry. To demonstrate its usefulness, we studied PCs during storage. PCs were prepared by apheresis technique (N = 7).Metabolic variables and platelet function was measured on day 1, 5, 7 and 12 of storage.Spontaneous and TRAP-6-induced adhesion to fibrinogen-and collagen-coated beads was analysed by flow cytometry. P-selectin and phosphatidyl serine (PS) expression was assessed on platelets bound to beads as well as on non-adherent platelets. Platelet adhesion to fibrinogen beads had increased by day 12 and adhesion to collagen beads at day 7 of storage (p < 0.05). TRAP-6 stimulation significantly increased the platelet adhesion to fibrinogen beads (p < 0.05) as well as the P-selectin and PS exposure on platelets bound to beads (p < 0.01) during the first 7 days of storage, but by day 12, significant changes were no longer induced by TRAP-6 stimulation.We demonstrate that our adhesion assay using protein-coated polystyrene beads can be used to assess the adhesion properties of platelets during storage without the addition of red blood cells. Therefore it may offer a useful tool for future studies of platelet adhesive capacity in transfusion medicine and other settings.3

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Section: Discussionsupporting

confidence: 93%

Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads

et al. 2014

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“…2,5,8,13 Over the past decade it has been recognized that apoptosis also occurs in anucleated cytoplasts [14][15][16] and platelets. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] In contrast to nucleated cells, where the pivotal role of the mitochondrion in the control of apoptosis is well documented, the role of mitochondrial control of apoptosis in platelets is largely unknown. Although platelets lack a nucleus and nuclear DNA, they do contain mitochondria and mitochondrial DNA [32][33][34] and metabolically stable mRNA and are capable of protein synthesis.…”

mentioning

confidence: 99%

“…32 We have shown that diverse stimuli induce DCm depolarization in platelets, including the soluble platelet agonists thrombin 26,28 and calcium ionophore A23187, 24,26 antiglycoprotein (GP) IIb antibody, 27 pathologically high shear stresses 24 and long-term incubation of platelets under blood banking conditions. 26,31 Others, using rabbit and dog models, have shown the decrease of DCm in circulating platelets during aging of platelets in vivo. 25,38 Mitochondria-associated apoptotic markers, caspase-9 and proapoptotic members of Bcl-2 family, as well as activation of executioner caspase-3 have also been shown to be induced in human and mouse platelets both in vitro and in vivo under an appropriate stimulation.…”

mentioning

confidence: 99%

Mitochondrial control of platelet apoptosis: effect of cyclosporin A, an inhibitor of the mitochondrial permeability transition pore

Leytin

Allen

Mutlu

et al. 2009

Laboratory Investigation

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The role of the mitochondrial permeability transition pore (MPTP) in apoptosis of nucleated cells is well documented. In contrast, the role of MPTP in apoptosis of anucleated platelets is largely unknown. The aim of this study was to elucidate the contribution of MPTP in the control of different manifestations of platelet apoptosis by analyzing the effect of cyclosporin A (CsA), a potent inhibitor of MPTP formation. Using flow cytometry, we studied the effect of pretreatment of platelets with CsA on apoptotic responses in human platelets stimulated with calcium ionophore A23187. We found that CsA inhibited A23187-stimulated platelet apoptosis, completely preventing (i) depolarization of mitochondrial inner membrane potential (DCm), (ii) activation of cytosolic apoptosis executioner caspase-3, (iii) platelet shrinkage, and (iv) fragmentation of platelets to microparticles, but (v) only partially (E25%), inhibiting phosphatidylserine (PS) exposure on the platelet surface. This study shows that MPTP formation is upstream of DCm depolarization, caspase-3 activation, platelet shrinkage and microparticle formation, and stringently controls these apoptotic events in A23187-stimulated platelets but is less involved in PS externalization. These data also indicate that CsA may rescue platelets from apoptosis, preventing caspase-3 activation and inhibiting the terminal cellular manifestations of platelet apoptosis, such as platelet shrinkage and degradation to microparticles. Furthermore, the results suggest a novel potentially useful application of CsA as an inhibitor of platelet demise through apoptosis in thrombocytopenias associated with enhanced platelet apoptosis.

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“…Trombosit aktivasyonu ve apoptozu benzer özellikler gösterirler (PS translokasyonu, mikropartikül oluşumu gibi) ki bu durum trombosit aktivasyonunun apoptoza ilerlediğini düşündür-mektedir (28,29). Ancak, trombosit apoptozunun ve aktivasyonunun birbirinden farklı ilerleyebileceğini gösteren çalış-malar da mevcuttur (30).…”

Section: Discussionunclassified

Demir (III) varliginda trombosit gamaglutamil transferazinin pro-oksidan etkisi

Şener¹,

Çevik²,

Demirel³

et al. 2011

mpj

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Platelet activation and apoptosis are different phenomena: evidence from the sequential dynamics and the magnitude of responses during platelet storage

Cited by 57 publications

References 11 publications

Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads

Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads

Mitochondrial control of platelet apoptosis: effect of cyclosporin A, an inhibitor of the mitochondrial permeability transition pore

Demir (III) varliginda trombosit gamaglutamil transferazinin pro-oksidan etkisi

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