RBC‐derived vesicles during storage: ultrastructure, protein composition, oxidation, and signaling components

Kriebardis, Anastasios G.; Antonelou, Marianna H.; Stamoulis, Konstantinos; Economou-Petersen, Effrosini; Margaritis, Lukas H.; Papassideri, Issidora S.

doi:10.1111/j.1537-2995.2008.01794.x

Cited by 175 publications

(237 citation statements)

References 53 publications

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“…The membrane of these microparticles is known to contain many of the same components as the membrane of red blood cells, including lipid raft proteins (56). In our fast time-resolved photolysis experiments of NO uptake by red cell microparticles, we have measured that they scavenge NO ϳ3 times slower (1.81 ϫ 10 7 M Ϫ1 s Ϫ1 ) than cell-free Hb (5 ϫ 10 7 M Ϫ1 s Ϫ1 ).…”

Section: Discussionmentioning

confidence: 88%

“…Unlike phospholipid vesicles, these microparticles still have lipid raft proteins and other components characteristic of red cells in their membrane (56). Our simulations show that, in our fast time-resolved kinetic measurements of NO scavenging by red cell microparticles under aerobic conditions, membrane permeability mostly likely limits the reaction rate.…”

Section: Hemoglobin (Hb)mentioning

confidence: 87%

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Mechanisms of Slower Nitric Oxide Uptake by Red Blood Cells and Other Hemoglobin-containing Vesicles

Azarov

Liu

Reynolds

et al. 2011

Journal of Biological Chemistry

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Nitric oxide (NO) acts as a smooth muscle relaxation factor and plays a crucial role in maintaining vascular homeostasis. NO is scavenged rapidly by hemoglobin (Hb). However, under normal physiological conditions, the encapsulation of Hb inside red blood cells (RBCs) significantly retards NO scavenging, permitting NO to reach the smooth muscle. The rate-limiting factors (diffusion of NO to the RBC surface, through the RBC membrane or inside of the RBC) responsible for this retardation have been the subject of much debate. Knowing the relative contribution of each of these factors is important for several reasons including optimization of the development of blood substitutes where Hb is contained within phospholipid vesicles. We have thus performed experiments of NO uptake by erythrocytes and microparticles derived from erythrocytes and conducted simulations of these data as well as that of others. We have included extracellular diffusion (that is, diffusion of the NO to the membrane) and membrane permeability, in addition to intracellular diffusion of NO, in our computational models. We find that all these mechanisms may modulate NO uptake by membrane-encapsulated Hb and that extracellular diffusion is the main ratelimiting factor for phospholipid vesicles and erythrocytes. In the case of red cell microparticles, we find a major role for membrane permeability. These results are consistent with prior studies indicating that extracellular diffusion of several gas ligands is also rate-limiting for erythrocytes, with some contribution of a low membrane permeability. Hemoglobin (Hb)2 encapsulated within red blood cells scavenges NO at a significantly slower rate than hemoglobin that is freely dissolved within blood plasma (cell-free Hb) (1-4). A similar effect is observed for the uptake of oxygen (5-7). This reduction in the scavenging rate allows NO that is produced in the endothelial cells within the walls of blood vessels to diffuse to the smooth muscle in sufficient concentrations to activate soluble guanylate cyclase (8 -12), which would not be possible otherwise (13). NO thus effectively functions as a smooth muscle relaxant under normal physiological conditions. The reasons for the reduction of the rate of NO scavenging by red cell-encapsulated versus cell-free Hb have been extensively investigated and yet this remains a debated subject. The difference in the scavenging rates has been attributed to four possible factors: 1) a red blood cell (RBC)-free zone adjacent to the endothelium due to the velocity gradient in laminar flow (2-4), 2) NO uptake being rate-limited by diffusion of NO to the RBC, which contributes to the phenomenon of an unstirred layer around the RBC (1, 6, 14 -16), 3) an intrinsic, physical RBC membrane barrier to NO diffusion (14,(17)(18)(19)(20), and 4) NO uptake being rate-limited by diffusion of NO within the RBC (intracellular diffusion) (17, 21). Although there is no disagreement about the effect of the RBC-free zone along the endothelium on reducing NO reaction rates with red cell hem...

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Section: Discussionmentioning

confidence: 88%

Section: Hemoglobin (Hb)mentioning

confidence: 87%

Mechanisms of Slower Nitric Oxide Uptake by Red Blood Cells and Other Hemoglobin-containing Vesicles

Azarov

Liu

Reynolds

et al. 2011

Journal of Biological Chemistry

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“…Free radicals and intermediate peroxidation products damage the integrity and functioning of the membrane [47][48][49]. Lipids (cholesterol, polyunsaturated fatty acids (PUFA)) are the main targets of oxidative attack and this leads to the formation and the accumulation of lipid peroxidation (LPO) products [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes

Ravikumar

Hsieh

Vani

2015

Indian J Hematol Blood Transfus

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Erythrocytes undergo various changes during storage (storage lesion) that in turn reduces their functioning and survival. Oxidative stress plays a major role in the storage lesion and antioxidants can be used to combat this stress. This study elucidates the effects of L-carnitine (LC) on erythrocytes of stored blood. Blood was obtained from male Wistar rats and stored (4°C) for 20 days in CPDA-1 (citrate phosphate dextrose adenine) solution. Samples were divided into-(i) controls (ii) LC 10 (L-carnitine at a concentration of 10 mM) (iii) LC 30 (L-carnitine at a concentration of 30 mM) and (iv) LC 60 (L-carnitine at a concentration of 60 mM). Every fifth day, the biomarkers (haemoglobin, hemolysis, antioxidant enzymes, lipid peroxidation and protein oxidation products) were analysed in erythrocytes. Hemoglobin and protein sulfhydryls were insignificant during storage indicative of the maintenance of hemoglobin and sulfhydryls in all groups. Superoxide dismutase and malondialdehyde levels increased initially and decreased towards the end of storage. The levels of catalase and glutathione peroxidase were lower in experimentals than controls during storage. L-carnitine assisted the enzymes by scavenging the reactive oxygen species produced. Hemolysis increased in all groups with storage, elucidating that L-carnitine could not completely protect lipids and proteins from oxidative stress. Hence, this study opens up new avenues of using L-carnitine as a component of storage solutions with combinations of antioxidants in order to maintain efficacy of erythrocytes.

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“…Hence, at the level of the RBC membrane split and connect events can occur easily and sometimes are spontaneous, e.g., vesiculation during blood storage. 8 At the level of the whole cell, erythrocyte behavior in a pore is similar to the one observed for liquid droplets passing through microchannels. To estimate the physical regimes, which are guiding the process, several flow properties were estimated (see Table II).…”

Section: -7mentioning

confidence: 63%

“…[5][6][7] The vesiculation of RBCs during blood storage is often observed. 8 Locally, the erythrocyte membrane deforms due to pH changes. 9 Several methods were implemented to measure erythrocyte membrane properties: AFM, 10 SEM, 11 high frequency electric field, 12 optical tweezers, 13 and micropipette experiments with actin filaments visualizations.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of red blood cells in microporous membranes

2014

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We have performed microfluidic experiments with erythrocytes passing through a network of microchannels of 20-25 lm width and 5 lm of height. Red blood cells (RBCs) were flowing in countercurrent directions through microchannels connected by lm pores. Thereby, we have observed interesting flow dynamics. All pores were blocked by erythrocytes. Some erythrocytes have passed through pores, depending on the channel size and cell elasticity. Many RBCs split into two or more smaller parts. Two types of splits were observed. In one type, the lipid bilayer and spectrin network were cut at the same time. In the second type, the lipid bilayer reconnected, but the part of spectrin network stayed outside the cell forming a rope like structure, which could eventually break. The microporous membrane results in multiple breakups of the cells, which can have various clinical implications, e.g., glomerulus hematuria and anemia of patients undergoing dialysis. The cell breakup procedure is similar to the one observed in the droplet breakage of viscoelastic liquids in confinement. V C 2014 AIP Publishing LLC.

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RBC‐derived vesicles during storage: ultrastructure, protein composition, oxidation, and signaling components

Abstract: These data indicate that the vesicles released during storage of RBCs contain lipid raft proteins and oxidized or reactive signaling components commonly associated with the senescent RBCs. Vesiculation during storage of RBCs may enable the RBC to shed altered or harmful material.

Cited by 175 publications

References 53 publications

Mechanisms of Slower Nitric Oxide Uptake by Red Blood Cells and Other Hemoglobin-containing Vesicles

Mechanisms of Slower Nitric Oxide Uptake by Red Blood Cells and Other Hemoglobin-containing Vesicles

l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes

Dynamics of red blood cells in microporous membranes

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