Previous Cryopreservation Alters the Natural History of the Red Blood Cell Storage Lesion

Chang, Alex L.; Hoehn, Richard S.; Jernigan, Peter L.; Cox, Daniel; Schreiber, Martin A.; Pritts, Timothy A.

doi:10.1097/shk.0000000000000668

Cited by 26 publications

(21 citation statements)

References 30 publications

(29 reference statements)

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“…The sensitivity to stimuli of eryptosis may be enhanced in several clinical conditions, such as dehydration [58], hyperphosphatemia [59], chronic kidney disease (CKD) [60][61][62][63], hemolytic-uremic syndrome [64], diabetes [65], hepatic failure [66], malignancy [5], sepsis [67], sickle-cell disease [5], beta-thalassemia [5], Hb-C and G6PD-deficiency [5], as well as Wilsons disease [68]. The sensitivity to triggers of eryptosis is further a function of erythrocyte age [5,[69][70][71][72][73].…”

Section: Discussionmentioning

confidence: 99%

Triggering of Suicidal Erythrocyte Death by Fascaplysin

Mischitelli

Jèmaà

Almasry

et al. 2016

Cell Physiol Biochem

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Background/Aims: The bis-indole alkaloid Fascaplysin is effective against malignancy, an effect at least partially due to stimulation of tumor cell apoptosis. Similar to apoptosis of nucleated cells, erythrocytes could enter suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), oxidative stress and ceramide. The present study explored, whether Fascaplysin induces eryptosis and, if so, to shed light on the cellular mechanisms involved. Methods: Flow cytometry was employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was quantified from the hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to Fascaplysin (≥ 5 µM) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter, and significantly increased Fluo3-fluorescence, DCFDA fluorescence as well as ceramide abundance. The effect of Fascaplysin on annexin-V-binding and forward scatter was significantly blunted but not abolished by removal of extracellular Ca²⁺. Conclusions: Fascaplysin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca²⁺ entry, oxidative stress and ceramide.

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Section: Discussionmentioning

confidence: 99%

Triggering of Suicidal Erythrocyte Death by Fascaplysin

Mischitelli

Jèmaà

Almasry

et al. 2016

Cell Physiol Biochem

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“…Moreover, eryptosis is enhanced in elderly individuals [64]. It is sensitive to erythrocyte age [65] and enhanced eryptosis is observed following erythrocyte storage [66, 67]. …”

Section: Introductionmentioning

confidence: 99%

Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

Abed

Thiel

Towhid

et al. 2017

Cell Physiol Biochem

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Background: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca²⁺-activity ([Ca²⁺]_i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies. Moreover, blood was drawn from patients with acute appendicitis (9♀,11♂) and healthy volunteers (10♀,10♂) for determination of CRP, blood count and phosphatidylserine. Results: A 48h CRP treatment significantly increased the percentage of annexin-V-binding cells (≥5µg/ml), [Ca²⁺]_i (≥5µg/ml), ceramide (20µg/ml) and caspase-activity (20µg/ml). Annexin-V-binding was significantly blunted by caspase inhibitor zVAD (10µM). The percentage of phosphatidylserine-exposing erythrocytes in freshly drawn blood was significantly higher in appendicitis patients (1.83±0.21%) than healthy volunteers (0.81±0.09%), and significantly higher following a 24h incubation of erythrocytes from healthy volunteers to patient plasma than to plasma from healthy volunteers. The percentage of phosphatidylserine-exposing erythrocytes correlated with CRP plasma concentration. Conclusion: C-reactive protein triggers eryptosis, an effect at least partially due to increase of [Ca²⁺]_i, increase of ceramide abundance and caspase activation.

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“…24,25 A unique device allowing rapid screening for both membrane and haemoglobin disorders may be also of particular interest in lowand middle-income countries especially.…”

Section: Discussionmentioning

confidence: 99%