Microvesicules

Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we focus on plasma membrane-derived microvesicles (MVs), far less appreciated than exosomes. We integrate documented mechanisms involved in MV biogenesis and shedding, focusing on the red blood cell as a model...

BACKGROUND: Ex vivo cold storage of red blood cells (RBCs) for transfusion has long been associated with hypothermic storage lesions. It has been proposed that liposomes can be used to mitigate hemorheological elements of RBC membrane storage lesions. This study aimed to determine the appropriate liposome treatment time and assess the effects of liposome treatment on RBC's hemorheological and metabolic profiles. MATERIALS AND METHODS: Unilamellar liposomes were synthesized to contain a bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC):cholesterol (7:3 mol%)...

The storage of erythrocyte concentrates (ECs) induces lesions that notably affect metabolism, protein activity, deformability of red blood cells (RBCs), as well as the release of oxygen. Band 3 is one of the proteins affected during the ex vivo aging of RBCs. This membrane protein is an anion transporter, an anchor site for the cytoskeleton and other membrane proteins as well as a binding site for glycolytic enzymes and bears blood group antigens. In the present study, band 3 complexes were isolated from RBCs stored for 7 and 42 days in average ( n = 3), as well as from microvesicles ( n = 3)...

In response to collagen stimulation, platelets use a coordinated system of fluid entry to undergo membrane ballooning, procoagulant spreading, and microvesiculation. We hypothesized that water entry was mediated by the water channel aquaporin-1 (AQP1) and aimed to determine its role in the platelet procoagulant response and thrombosis. We established that human and mouse platelets express AQP1 and localize to internal tubular membrane structures. However, deletion of AQP1 had minimal effects on collagen-induced platelet granule secretion, aggregation, or membrane ballooning...

Platelets storage lesion is mainly orchestrated by platelet activating signals during storage. Reactive oxygen species (ROS) are being considered as important signaling molecules modulating platelet function while their production has also been shown to be augmented by platelet activation. This study investigated to what extent endogenous ROS generation during platelet storage could be correlated with platelet receptor shedding, microvesiculation and adhesive function. 10 PRP-platelet concentrates were subjected to flow cytometry analysis to examine the generation of intraplatelet ROS on days 1, 5 and 7 after storage...

A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules on the volar wrists, extensor elbows, and bilateral lower legs of 3 years' duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months' duration. She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. Workup revealed lichen planus pemphigoides (LPP), a rare papulosquamous and vesiculobullous dermatosis that shares features of both lichen planus (LP) and bullous pemphigoid (BP)...

DIC is a severe complication, often resulting in multi-organ failure and fatal outcome. As any syndrome, it is polyethiologic, while a big number of its causes logically leads to various mechanisms of its forming. Main manifestations of the disseminated intravascular blood coagulation syndrome are clottage and haemorrhage. A result of a massive clottage in microcirculatory bed of internal organs is development of dystrophic changes in them and organ failure. Haemorrhage in its turn, results in decreased volume of circulating blood, arterial hypotension and hemic hypoxia, in most severe cases leading to the fatal outcome...

Hemodiafiltration (HDF) is a renal replacement therapy that 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 effects on red blood cell (RBC) physiological features have not been examined in depth. In this study, ESRD patients under regular HDF or conventional hemodialysis (cHD) treatment were examined for RBC-related parameters, including anemia, hemolysis, cell shape, redox status, removal signaling, membrane protein composition, and microvesiculation, in repeated paired measurements accomplished before and right after each dialysis session...

Human platelet transformation into balloons is part of the haemostatic response and thrombus architecture. Here we reveal that in aggregates of platelets in plasma, ballooning in multiple platelets occurs in a synchronised manner. This suggests a mechanism of coordination between cells, previously unrecognised. We aimed to understand this mechanism, and how it may contribute to thrombus development. Using spinning-disc confocal microscopy we visualised membrane ballooning in human platelet aggregates adherent to collagen-coated surfaces...

BACKGROUND: Red blood cells collected in citrate-phosphate-dextrose can be stored for up to 42 days at 4 °C in saline-adenine-glucose-mannitol additive solution. During this controlled, but nevertheless artificial, ex vivo ageing, red blood cells accumulate lesions that can be reversible or irreversible upon transfusion. The aim of the present study is to follow several parameters reflecting cell metabolism, antioxidant defences, morphology and membrane dynamics during storage. MATERIALS AND METHODS: Five erythrocyte concentrates were followed weekly during 71 days...

γ-Irradiation of red blood cell (RBC) concentrates prevents transfusion-associated graft-versus-host disease but may diminish RBC quality. Herein, we show that early γ-irradiation (25 Gy) of RBC units and their subsequent storage in SAG-M additive solution altered membrane microvesiculation, supernatant haemoglobin and cytosolic ATP. γ-Irradiation did not influence phosphatidylserine externalization, a marker of erythrocyte apoptotic cell death (eryptosis), in RBC stored for 42 days. However, shorter periods (4-21 days) of storage accentuated eryptosis in γ-irradiated RBC versus untreated RBCs following energy depletion, suggesting that γ-irradiated RBC is primed for stress-induced eryptosis during storage...

OBJECTIVE: Modified, bioreactive red blood cells (RBCs) and RBC-derived microvesicles (MVs) likely contribute to the hematological and cardiovascular complications in end-stage renal disease (ESRD). This study assesses the physiological profile of RBCs in patients with ESRD receiving standard or high doses of recombinant human erythropoietin (rhEPO). METHOD: Blood samples from twenty-eight patients under sustained hemodialysis, responsive, or not to standard rhEPO administration were examined for RBC morphology, fragility, hemolysis, redox status, removal signaling, membrane protein composition, and microvesiculation before and after dialysis...

BACKGROUND: Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life...

INTRODUCTION: Hemorheological disorders play an important part in pathogenesis of acute period of burn injury. This mechanism remains practically unstudied. Thus, unknown is the role of hemoglobin glycation and erythrocyte microvesiculation in the decrease in erythrocyte deformability after thermal trauma. METHODS: Research was performed on 30 blood samples of burn patients in the acute period and 40 blood samples of healthy donors. The number of erythrocyte-derived microvesicles was determined by flow cytometry and then standardized in the samples; the microvesicles were preliminarily separated by ultracentrifugation at 100,000 g, for 60 minutes...

To date, the development of bioreactors for the study of red blood cells (RBCs, daily transfused in the case of disease or hemorrhage) has focused on hematopoietic stem cells. Despite the fact that mature RBCs are enucleated and do not expand, they possess complex cellular and metabolic pathways, as well as post-translation modification signaling and gas-exchange regulation. In order to dynamically study the behavior of RBCs and their signaling pathways under various conditions, a small-scale perfusion bioreactor has been developed...

CONTEXT: Liposomes have been shown to improve human red blood cell (RBC) in vitro quality by minimizing membrane damage occurring during 42-d hypothermic storage. Small animal models are necessary to evaluate novel blood products and guide future clinical studies. OBJECTIVES: The aim of this study was to assess the effect of liposome treatments on rat RBC hypothermic storage lesion (HSL) and to examine in vivo outcomes of transfusing liposome treated RBCs in a rat model...

BACKGROUND: Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. OBJECTIVE: We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen...

Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophil-derived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis...

BACKGROUND: Platelets are central to the process of hemostasis, rapidly aggregating at sites of blood vessel injury and acting as coagulation nidus sites. On interaction with the subendothelial matrix, platelets are transformed into balloonlike structures as part of the hemostatic response. It remains unclear, however, how and why platelets generate these structures. We set out to determine the physiological relevance and cellular and molecular mechanisms underlying platelet membrane ballooning...

Microvesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown that microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In cells treated with docetaxel (DTX), this inhibition resulted in a third-fold increase in intracellular concentrations of DTX...