Red Blood Cell Homeostasis: Mechanisms and Effects of Microvesicle Generation in Health and Disease

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.

Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

“…The fraction of the most mature reticulocytes, as detected by the fraction of CD71-positive RBCs [20], decreased after the first day of marching, but increased again during the consecutive night ( Figure 3). RBC aging is accompanied by the generation of microvesicles [24]. In the blood of the Four Days Marches participants, we found no significant changes in RBC-derived microvesicle concentrations.…”

Complement activation during intravascular hemolysis: Implication for sickle cell disease and hemolytic transfusion reactions

“…Generation of MVs, i.e., extracellular vesicles that are shed from the plasma membrane, constitutes an integral part of RBC homeostasis, but this process is exacerbated in pathological conditions such as SCD (114). Novel discoveries on MVs from RBC, their ability to disseminate into the bloodstream and to modulate inflammation and coagulation have opened up a new field of investigation.…”

Red blood cells: the forgotten player in hemostasis and thrombosis

“…Pro [18][19][20][21][22][23][24][25] RBCs release membrane-derived procoagulant microvesicles bearing phosphatidylserine during in vivo aging and in vitro storage Pro [28][29][30][31]33,34] Meizothrombin, a protein C activator with low fibrinogen-cleaving activity, is formed on RBCs and released into the blood Anti [20] Factor IX is activated directly by an elastase-like enzyme on the RBC Pro [31,32,34,36,37,[40][41][42][43][44][45][47][48][49] Quantitative and qualitative changes in RBCs related to bleeding and thrombosis…”