Abstract
Red blood cells (RBCs) generate microvesicles to remove damaged cell constituents such as oxidized hemoglobin and damaged membrane constituents, and thereby prolong their lifespan. Damage to hemoglobin, in combination with altered phosphorylation of membrane proteins such as band 3, lead to a weakening of the binding between the lipid bilayer and the cytoskeleton, and thereby to membrane budding and microparticle shedding. Microvesicle generation is disturbed in patients with RBC-centered diseases, such as sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, spherocytosis or malaria. A disturbance of the membrane-cytoskeleton interaction is likely to be the main underlying mechanism, as is supported by data obtained from RBCs stored in blood bank conditions. A detailed proteomic, lipidomic and immunogenic comparison of microvesicles derived from different sources is essential in the identification of the processes that trigger vesicle generation. The contribution of RBC-derived microvesicles to inflammation, thrombosis and autoimmune reactions emphasizes the need for a better understanding of the mechanisms and consequences of microvesicle generation.
Highlights
Generation of microvesicles, i.e., extracellular vesicles that are shed from the plasma membrane (Raposo and Stoorvogel, 2013), constitutes an integral part of red blood cell (RBC) homeostasis, and is responsible for the loss of 20% of the hemoglobin and the cell membrane during physiological Red blood cells (RBCs) aging in vivo, and the accompanying decrease in cell volume and increase in cell density (Willekens et al, 2003, 2008)
In RBCs from patients with thalassemia intermedia, hemoglobin damage may induce the formation of band 3 polymers, associated with increased phosphorylation that leads to a weakening of the band 3-ankyrin connection, resulting in microvesicle formation (Ferru et al, 2014)
The involvement of various signaling pathways in RBC vesiculation was supported by the relative large numbers of signaling proteins in microvesicles obtained from the plasma of a healthy donor (Bosman et al, 2012), and in a pharmacological screening in vitro (Kostova et al, 2015)
Summary
Generation of microvesicles, i.e., extracellular vesicles that are shed from the plasma membrane (Raposo and Stoorvogel, 2013), constitutes an integral part of red blood cell (RBC) homeostasis, and is responsible for the loss of 20% of the hemoglobin and the cell membrane during physiological RBC aging in vivo, and the accompanying decrease in cell volume and increase in cell density (Willekens et al, 2003, 2008). We aim to integrate the newest data on microvesicle composition and production in various conditions, in order to obtain more insight into the basic mechanisms underlying microvesicle generation, and the involvement of RBC-derived microvesicles in pathophysiology
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