Bacterial neuraminidase‐mediated erythrocyte desialylation provokes cell surface aminophospholipid exposure

Qadri, Syed M.; Donkor, David A.; Nazy, Ishac; Branch, Donald R.; Sheffield, William P.

doi:10.1111/ejh.13047

Cited by 8 publications

(3 citation statements)

References 50 publications

(132 reference statements)

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“…RBC cell death has been documented from a wide variety of pathological stressors and in association with multiple human diseases [30]. Other potential explanations for accelerated loss of RBCs in the infected patients include exposure to reactive oxygen species [31], neuraminidases [17,32] and histones [33] formed either by pathogens or by host cells and by stimulation of purinergic signalling in RBCs [34].…”

Section: Discussionmentioning

confidence: 99%

A positive blood culture is associated with a lower haemoglobin increment in hospitalized patients after red blood cell transfusion

et al. 2022

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Background and Objectives Abundant clinical evidence supports the safety of red blood cell (RBC) concentrates for transfusion irrespective of storage age, but still, less is known about how recipient characteristics may affect post‐transfusion RBC recovery and function. Septic patients are frequently transfused. We hypothesized that the recipient environment in patients with septicaemia would blunt the increase in post‐transfusion blood haemoglobin (Hb). The main objective was to compare the post‐transfusion Hb increment in hospitalized patients with or without a positive blood culture. Materials and Methods A retrospective cohort study using data from the Transfusion Research, Utilization, Surveillance, and Tracking database (TRUST) was performed. All adult non‐trauma in‐patients transfused between 2010 and 2017 with ≥1 RBC unit, and for whom both pre‐ and post‐transfusion complete blood count and pre‐transfusion blood culture data were available were included. A general linear model with binary blood culture positivity was fit for continuous Hb increment after transfusion and was adjusted for patient demographic parameters and transfusion‐related covariates. Results Among 210,263 admitted patients, 6252 were transfused: 596 had positive cultures, and 5656 had negative blood cultures. A modelled Hb deficit of 1.50 g/L in blood culture‐positive patients was found. All covariates had a significant effect on Hb increment, except for the age of the transfused RBC. Conclusion Recipient blood culture positivity was associated with a statistically significant but modestly lower post‐transfusion Hb increment in hospitalized patients. In isolation, the effect is unlikely to be clinically significant, but it could become so in combination with other recipient characteristics.

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Section: Discussionmentioning

confidence: 99%

A positive blood culture is associated with a lower haemoglobin increment in hospitalized patients after red blood cell transfusion

et al. 2022

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“…Hypercoagulation is a well-known hallmark of inflammation 40 and is caused by pathological levels of circulating inflammatory molecules, including pro-inflammatory cytokines 36 . Importantly, during inflammation, erythrocytes (RBCs) and platelets are also involved in the pathological clotting process, where circulating mediators of inflammation cause the membranes of these cells to become altered into procoagulant surfaces 41 – 46 . Also, it was recently reported that von Willebrand factor plays a role in erythrocyte endothelial adhesion, where eryptotic erythrocytes may interact with von Willebrand factor fibres 47 .…”

Section: Introductionmentioning

confidence: 99%

Correlative Light-Electron Microscopy detects lipopolysaccharide and its association with fibrin fibres in Parkinson’s Disease, Alzheimer’s Disease and Type 2 Diabetes Mellitus

Waal

Engelbrecht

Davis

et al. 2018

Sci Rep

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Many chronic diseases, including those classified as cardiovascular, neurodegenerative, or autoimmune, are characterized by persistent inflammation. The origin of this inflammation is mostly unclear, but it is typically mediated by inflammatory biomarkers, such as cytokines, and affected by both environmental and genetic factors. Recently circulating bacterial inflammagens such as lipopolysaccharide (LPS) have been implicated. We used a highly selective mouse monoclonal antibody to detect bacterial LPS in whole blood and/or platelet poor plasma of individuals with Parkinson’s Disease, Alzheimer’s type dementia, or Type 2 Diabetes Mellitus. Our results showed that staining is significantly enhanced (P < 0.0001) compared to healthy controls. Aberrant blood clots in these patient groups are characterized by amyloid formation as shown by the amyloid-selective stains thioflavin T and Amytracker™ 480 or 680. Correlative Light-Electron Microscopy (CLEM) illustrated that the LPS antibody staining is located in the same places as where amyloid fibrils may be observed. These data are consistent with the Iron Dysregulation and Dormant Microbes (IDDM) hypothesis in which bacterial inflammagens such as LPS are responsible for anomalous blood clotting as part of the aetiology of these chronic inflammatory diseases.

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“…Signaling mechanisms inhibiting eryptosis include the kinases AMPK [12], cGMP-dependent protein kinase [12], MSK1/2 [23], PAK2 [12] and sorafenib/sunitinib sensitive kinases [12]. Eryptosis is stimulated by a wide variety of xenobiotics [12, and enhanced eryptosis is observed in several clinical conditions including iron deficiency [12], dehydration [78], hyperphosphatemia [68], vitamin D excess [32], chronic kidney disease (CKD) [79][80][81][82][83] hemolytic-uremic syndrome [84], diabetes [85], hepatic failure [86,87], malignancy [88,89], autoimmune hemolytic anemia [90], lack of sialic acid [91], arteriitis [92], sepsis [93], sickle-cell disease [12], beta-thalassemia [12], Hb-C and G6PD-deficiency [12], Wilsons disease [94], as well as advanced age [95]. Eryptosis further increases following storage for transfusion [96][97][98].…”

Section: Introductionmentioning

confidence: 99%

Sonidegib, a Novel Inhibitor of Suicidal Erythrocyte Death

Bhuyan¹,

Sahu²,

Cao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Hedgehog pathway disrupting drug sonidegib is used in the treatment of basal cell carcinoma. Side effects of sonidegib include anemia, which could result either from impaired erythropoiesis or from loss of erythrocytes e.g. due to suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Eryptosis is stimulated by cell stress, including energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i). The present study explored, whether sonidegib exerts an effect on eryptosis. Methods: Human erythrocytes have been treated with energy depletion (glucose withdrawal for 48 hours), hyperosmotic shock (addition of 550 mM sucrose for 6 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca²⁺ ionophore ionomycin (1 µM for 60 min) in absence and presence of sonidegib (2-6 µg/ ml). After treatment flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, and cell volume from forward scatter. Hemolysis was estimated from the hemoglobin concentration in the supernatant. Results: In the absence of cell stress exposure to sonidegib did not significantly modify annexin-V-binding or forward scatter, but triggered hemolysis. Energy depletion, hyperosmotic shock, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. Sonidegib significantly blunted the effect of energy depletion, hyperosmotic shock, and oxidative stress, but not of ionomycin on annexin-V-binding. Sonidegib further significantly blunted the effect of energy depletion, but not of hyperosmotic shock, oxidative stress, and ionomycin on forward scatter. Conclusions: Sonidegib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion, hyperosmotic shock and oxidative stress.

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Bacterial neuraminidase‐mediated erythrocyte desialylation provokes cell surface aminophospholipid exposure

Abstract: Collectively, our data reveal that alteration of erythrocyte sialylation status by bacterial neuraminidase favors eryptotic cell death, an effect potentially contributing to reduced erythrocyte lifespan and anemia in sepsis.

Cited by 8 publications

References 50 publications

A positive blood culture is associated with a lower haemoglobin increment in hospitalized patients after red blood cell transfusion

A positive blood culture is associated with a lower haemoglobin increment in hospitalized patients after red blood cell transfusion

Correlative Light-Electron Microscopy detects lipopolysaccharide and its association with fibrin fibres in Parkinson’s Disease, Alzheimer’s Disease and Type 2 Diabetes Mellitus

Sonidegib, a Novel Inhibitor of Suicidal Erythrocyte Death

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