Marianna H. Antonelou

National and Kapodistrian University of Athens (NKUA) · Department of Biology

Oxidative phenomena are considered to lie at the root of the accelerated senescence observed in red blood cells (RBCs) stored under standard blood bank conditions. It was recently shown that the addition of uric (UA) and/or ascorbic acid (AA) to the preservative medium beneficially impacts the storability features of RBCs related to the handling of...

Redox imbalance and oxidative stress have emerged as generative causes of the structural and functional degradation of red blood cells (RBC) that happens during their hypothermic storage at blood banks. The aim of the present study was to examine whether the antioxidant enhancement of stored RBC units following uric (UA) and/or ascorbic acid (AA) s...

Mature red blood cells (RBC) are the most abundant host cell in our body [...].

The broad spectrum of beta-thalassemia (βThal) mutations may result in mild reduction (β ++), severe reduction (β +) or complete absence (β 0) of beta-globin synthesis. βThal heterozygotes eligible for blood donation are "good storers" in terms of red blood cell (RBC) fragility, proteostasis and redox parameters of storage lesion. However, it has n...

Microvesicles or ectosomes represent a major type of extracellular vesicles that are formed by outward budding of the plasma membrane. Typically, they are bigger than exosomes but smaller than apoptotic vesicles, although they may overlap with both in size and content. Their release by cells is a means to dispose redundant, damaged, or dangerous ma...

The 24-hour (24 h) post-transfusion survival of donor red blood cells (RBCs) is an important marker of transfusion efficacy. Nonetheless, within that period, donated RBCs may encounter challenges able to evoke rapid stress-responses. The aim of the present study was to assess the effect of exposure to plasma and body temperature upon stored RBCs un...

The clarification of donor variation effects upon red blood cell (RBC) storage lesion and transfusion efficacy may open new ways for donor-recipient matching optimization. We hereby propose a "triangular" strategy for studying the links comprising the transfusion chain - donor, blood product, recipient - as exemplified in two cohorts of control and...

Red blood cells (RBCs) release hemoglobin (Hb)-containing extracellular vesicles (EVs) throughout their lifespan in the circulation, and especially during senescence, by spleen-facilitated vesiculation of their membrane. During ex vivo aging under blood bank conditions, the RBCs lose Hb, both in soluble form and inside EVs that accumulate as a part...

Blood donors with beta-thalassemia traits (βThal +) have proven to be good "storers", since their stored RBCs are resistant to lysis and resilient against oxidative/proteotoxic stress. To examine the performance of these RBCs post-storage, stored βThal + and control RBCs were reconstituted in plasma donated from transfusion-dependent beta-thalassem...

Proteasomes are multi-catalytic complexes with important roles in protein control. Their activity in stored red blood cells (RBCs) is affected by both storage time and the donor’s characteristics. However, apart from their abundancy in the membrane proteome, not much is known about their topology, activity, and networking during the storage of RBCs...

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-t...

Background Transfusion research has recently focused on the discovery of red blood cell (RBC) storage capacity biomarkers and the elucidation of donor variation effects. This shift of focus can further strengthen personalization of transfusion therapy, by revealing probable links between donor biology, RBC storage lesion profile, and posttransfusio...

Prestorage filtration of blood to remove contaminating donor leukocytes and platelets has substantially increased the safety level of transfusion therapy. We have previously shown that leukoreduction has a mitigating effect on the storage lesion profile by lowering the extent of hemolysis and of RBC aging and removal phenotypes, including surface s...

Background: Increases in the red blood cell (RBC) degree of fatty acid desaturation are reported in response to exercise, aging, or diseases associated with systemic oxidant stress. However, no studies have focused on the presence and activity of fatty acid desaturases (FADS) in the mature RBC. Study design and methods: Steady state metabolomics...

Genetic characteristics of blood donors may impact the storability of blood products. Despite higher basal stress, red blood cells (RBCs) from eligible donors that are heterozygous for beta-thalassemia traits (βThal+) possess a differential nitrogen-related metabolism, and cope better with storage stress compared to the control. Nevertheless, not m...

Blood donor genetics and lifestyle affect the quality of red blood cell (RBC) storage. Heterozygotes for beta-thalassaemia (βThal+) constitute a non-negligible proportion of blood donors in the Mediterranean and other geographical areas. The unique haematological profile of βThal+ could affect capacity of enduring storage stress, however, the stora...

Background: Proteasomes are proteolytic complexes with prominent roles in the control of protein homeostasis and cellular viability. However, little is known about the effects of storage and glucose-6-phosphate dehydrogenase deficiency (G6PD-) on the activity and topology of red blood cell (RBC) proteasomes. Materials and methods: We investigate...

Secretory phospholipase-IIA A2 (sPLA2-IIA) is expressed in a variety of cell types under inflammatory conditions. Its presence in the bronchoalveolar lavage (BAL) fluid of patients with acute respiratory distress syndrome (ARDS) is associated with the severity of the injury. Exosomal type extracellular vesicles, (EVs), are recognized to perform int...

Background: Several factors contribute to the manifestation of red blood cell (RBC) storage lesions, with one of the most interesting being the "donor variation effect". Since many haematological characteristics of blood donors are sex-dependent, sex hormones and their age-dependent variation may affect the storage profile of RBCs. Materials and...

Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cells in body fluids and extracellular matrix. They function as signal transducers in intercellular communication, contributing to the maintenance of cell and tissue integrity. EVs biogenesis is deregulated in various pathologies, in structural and functional connecti...

BACKGROUND Despite universal administration of erythropoiesis‐stimulating agents, patients with end‐stage renal disease (ESRD) are at high risk for presenting persistent anemia. Due to ambiguities in optimal hemoglobin targets and evidence of recombinant human erythropoietin (EPO)‐related toxicity, an increase in blood transfusions has been observe...

Blood transfusion is an essential and irreplaceable part of modern medicine, as a therapeutic modality or additional support to other clinical therapies. Nevertheless, the entire procedure from blood collection to administration, absorbs a significant amount of resources and has a number of problems that need to be addressed. The paucity of donors,...

Notwithstanding the high safety level of the currently available blood for transfusion and the decreasing frequency of transfusion-related complications, administration of labile blood products to paediatric patients still poses unique challenges and considerations. The incidence of thalassaemia and sickle cell disease in the paediatric population...

Objective Transfusion of fresh frozen plasma (FFP) helps in maintaining the coagulation parameters in patients with acquired multiple coagulation factor deficiencies and severe bleeding. However, along with coagulation factors and procoagulant extracellular vesicles (EVs), numerous bioactive and probably donor-related factors (metabolites, oxidized...

Objective In glucose 6-phosphate dehydrogenase (G6PD) deficiency, decreased NADPH regeneration in the pentose phosphate pathway and subnormal levels of reduced glutathione result in insufficient antioxidant defense, increased susceptibility of red blood cells (RBCs) to oxidative stress, and acute hemolysis following exposure to pro-oxidant drugs an...

Metabolomic analysis of G6PD sufficient (control) and G6PD deficient (G6PD def.) leukoreduced red blood cell concentrates throughout the storage period in CPD-SAGM.

Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored RBC units is clinically relevant for transfused recipients. Leukoreduced RBCs from G6PD-normal or -deficient human volu...

Background: Previous investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxi...

Hemodiafiltration (HDF) is a renal replacement therapy which is based on the principles of diffusion and convection for the elimination of uremic toxins. A significant and increasing number of end stage renal disease (ESRD) patients are treated with HDF, even in the absence of definite and conclusive survival and anemia treatment data. However, its...

Red blood cells (RBCs) represent the most commonly used and best-studied natural carriers in the history of drug delivery. Their abundance and long circulation half-life, their great immune-biocompatibility and biodegradability profiles, along with the availability of well established protocols for their safe collection, ex vivo processing and qual...

Anemia is present in more than half of cancer patients and appears to be an independent prognostic factor of short- and long-term adverse outcomes. It increases in the advanced period of cancer and perioperatively, in patients with solid tumors who undergo surgery. As a result, allogeneic red blood cell (RBC) transfusion is an indispensable treatme...

Background: To preserve cellular integrity and avoid bacterial growth, storage and transfer of blood and blood products follow strict guidelines in terms of temperature control. We evaluated the impact of ineligible warming of whole blood donations on the quality of blood components. Material and methods: One-hundred and twenty units of whole bl...

Objective: Modified, bio-reactive red blood cells (RBCs) and RBC-derived microvesicles likely contribute to the hematological and cardiovascular complications in end-stage renal disease (ESRD). This study assesses the physiological profile of red blood cells (RBCs) in end-stage renal disease (ESRD) patients receiving standard or high doses of reco...

What is following the impressive progress that has been made? During the last couple of years several tremors have shaken the field of Transfusion Medicine. The epicentres of those tremors were located on novel insights into the RBC storage lesion, on emerging connections between storage lesion and post-transfusion performance and effects, and on a...

Red blood cell storage lesion (RSL) is a multifaceted biological phenomenon. It refers to deterioration in RBC quality that is characterized by lethal and sub-lethal, reversible and irreversible defects. RSL is influenced by prestorage variables and it might be associated with variable clinical outcomes. Optimal biopreservation conditions are expec...

Release of vesicles from cells is a universal biological system, an adaptive cellular response to endogenous or external physiological or stressful stimuli and a genius means for intercellular, inter-organ and even inter-organism communication. These secreted vesicles that are collectively designated extracellular vesicles (EVs) have increasingly a...

This article contains data on the variation in several physiological parameters of red blood cells (RBCs) donated by eligible glucose-6-phosphate dehydrogenase (G6PD) deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD+) cells. Intracellular reactive oxygen species (ROS) generation, cell frag...

Although the molecular pathways leading to the progressive deterioration of stored red blood cells (RBC storage lesion) and the clinical relevance of storage-induced changes remain uncertain, substantial donor-specific variability in RBC performance during storage and post-transfusion has been established ("donor-variation effect"). In-bag hemolysi...

Storage of packed red blood cells (RBCs) is associated with progressive accumulation of lesions, mostly triggered by energy and oxidative stresses, which potentially compromise the effectiveness of the transfusion therapy. Concerns arise as to whether glucose 6-phosphate dehydrogenase deficient subjects (G6PD-), ~5% of the population in the Mediter...

Background: Previous studies have shown that baseline hematologic characteristics concerning or influencing red blood cell (RBC) properties might affect storage lesion development in individual donors. This study was conducted to evaluate whether variation in hemolysis, microparticle accumulation, phosphatidylserine (PS) exposure, and other storag...

Anemia is the most common hematologic complication in end stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in...

Background: Extracellular vesicles or microparticles exhibiting procoagulant and thrombogenic activity may contribute to the haemostatic potential of fresh frozen plasma. Materials and methods: Fresh frozen plasma was prepared from platelet-rich plasma at 20 ºC (Group-1 donors) or directly from whole blood at 4 ºC (Group-2 donors). Each unit was...

Oxidative stress orchestrates a significant part of the red blood cell (RBC) storage lesion. Considering the tremendous interdonor variability observed in the "storability," namely, the capacity of RBCs to sustain the storage lesion, this study aimed at the elucidation of donor-specific factors that affect the redox homeostasis during the storage o...

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical...

Unlabelled: Chronic kidney disease is a risk factor for cardiovascular mortality. This study uncovers pieces of hematological and erythrocyte protein variability observed in end stage renal disease (ESRD) in relation to disease progression/duration and mortality. Using a variety of experimental approaches, erythropoietin/dialysis-treated patients...

In eukaryotes, the ubiquitin–proteasome machinery regulates a number of fundamental cellular processes through accurate and tightly controlled protein degradation pathways. We have, herein, examined the effects of proteasome functional disruption in Dmp53 +/+ (wild-type) and Dmp53 −/−Drosophila melanogaster fly strains through utilization of Bortez...

The introduction of pre-storage leukoreduction in the preparation of standard RBCs intended for transfusion provided significant improvement in the quality of labile products and their post transfusion viability and effects, although the literature data are controversial. To elucidate the issue of the probable leukoreduction effects on RBCs storage...

The objective of this study was to investigate the effects of two sources of electromagnetic fields (EMFs) on the proteome of cerebellum, hippocampus, and frontal lobe in Balb/c mice following long-term whole body irradiation. Three equally divided groups of animals (6 animals/group) were used; the first group was exposed to a typical mobile phone,...

We have showed that secretory Apolipoprotein J/Clusterin (sCLU) is down-regulated in senescent, stressed or diseased red blood cells (RBCs). It was hypothesized that sCLU loss relates to RBCs vesiculation, a mechanism that removes erythrocyte membrane patches containing defective or potentially harmful components. To investigate this issue we emplo...

Secretory Apolipoprotein J/Clusterin (sCLU) is a ubiquitously expressed chaperone that has been functionally implicated in several pathological conditions of increased oxidative injury, including aging. Nevertheless, the biological role of sCLU in red blood cells (RBCs) remained largely unknown. In the current study we identified sCLU as a componen...

This study was designed to evaluate the oxidative stress status of erythrocytes and its association with cellular ultrastructure and membrane proteome modifications in patients with end stage renal disease (ESRD) on hemodialysis (HD). For that purpose, we studied red blood cells' (RBCs) modifications in twelve non-diabetic ESRD patients that were r...

The red blood cells (RBCs) aging process is considered as an issue of special scientific and clinical interest. It represents a total of unidirectional, time-dependent but not-necessarily linear series of molecular events that finally lead to cell clearance1. Under normal circumstances, all human RBCs live approximately 120±4 days in blood circulat...

It has been suggested that red blood cell (RBC) senescence is accelerated under blood bank conditions, although neither protein profile of RBC aging nor the impact of additive solutions on it have been studied in detail. RBCs and vesicles derived from RBCs in both citrate-phosphate-dextrose (CPD)-saline-adenine-glucose-mannitol (SAGM) and citrate-p...

We investigated the protein carbonylation of red blood cell (RBC) membrane in type 2 diabetic patients and the potential implication of carbonyl/oxidative stress in reflecting disease severity. Sixty-four diabetic patients with or without retinopathy of variable clinical severity (Groups DR and DM, respectively) and 20 healthy controls were include...

Secretory clusterin (sCLU)/apolipoprotein J is an extracellular chaperone that has been functionally implicated in DNA repair, cell cycle regulation, apoptotic cell death, and tumorigenesis. It exerts a prosurvival function against most therapeutic treatments for cancer and is currently an antisense target in clinical trials for tumor therapy. Howe...

Red cells (RBCs) lose membrane in vivo, under certain conditions in vitro, and during the ex vivo storage of whole blood, by releasing vesicles. The vesiculation of the RBCs is a part of the storage lesion. The protein composition of the vesicles generated during storage of banked RBCs has not been studied in detail. Vesicles were isolated from the...

The elucidation of the storage lesion is important for the improvement of red blood cell (RBC) storage. Ex vivo storage is also a model system for studying cell-signaling events in the senescence and programmed cell death of RBCs. The membrane hosts critical steps in these mechanisms and undergoes widespread remodeling over the storage period. Fres...

Several rheological disorders of the erythrocytes, such as increased aggregation and decreased deformability, have been observed in diabetes mellitus and have been implicated in the development of diabetic microangiopathy. Structural alterations of the erythrocyte membrane proteins caused by the diabetic process may be at the origin of those observ...

Hereditary spherocytosis (HS) is a heterogeneous group of disorders. The abnormal red cell morphology (resulting in shortened cell survival) is due to a primary deficiency in spectrin, ankyrin-1, band 3 or protein 4.2. Secondary protein deficiencies are often observed and may be involved in the outcome of the disease. In the present study, we searc...