Hemoglobin oxidation–dependent reactions promote interactions with band 3 and oxidative changes in sickle cell–derived microparticles

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

“…Hx only partially decreased complement activation (56), in agreement with the complement-activating propensity of PS and PE (52). Moreover, incubation of SCD MVs with endothelial cells caused greater loss of monolayer integrity, apoptotic activation, heme oxygenase-1 induction, and concomitant bioenergetic imbalance compared with control MVs (116).…”

Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy

“…Moreover, treatment with HU correlated with even higher surface expression of CD46 on neutrophils. These results, together with the data from the literature, show that the beneficial effect of HU should be related to the %DRBCs, RBC microvesicles, the reduction of the activation state of the neutrophils and endothelial cells and posttranslational modifications of Hb and, hence, heme release, rather than direct effect of HU as a complement inhibitor . Indeed, HU‐treated patients showed reduced hemolysis and higher fetal Hb and heme‐scavenger hemopexin compared to NT patient .…”

Microvesicle Formation Induced by Oxidative Stress in Human Erythrocytes

“…Band 3 plays a significant role in RBC functions, and clustering of this protein was demonstrated in several RBCs disorders [ 7 , 21 , 23 ]. Additionally, band 3 clustering is one of important signals to eliminate senescent and pathological RBCs [ 49 ]; therefore, we next used an EMA test to elucidate the effects of the used compounds on band 3 clustering.…”

“…Additionally, band 3 clustering is one of important signals to eliminate senescent and pathological RBCs [ 49 ]; therefore, we next used an EMA test to elucidate the effects of the used compounds on band 3 clustering. Oxidative stress induces band 3 oxidation and dissociation from spectrin skeleton, resulting in enhanced mobility and subsequent band 3 cluster formation [ 21 , 23 , 49 ]. In our experiments, we tested whether each of the used compounds triggers band 3 clustering by applying the EMA-binding test.…”

“…Ca 2+ -activated protease calpain is involved in vesiculation by binding and degrading band 3, band 4.1, and ankyrin, which lead to alteration of cell deformability [ 9 , 16 , 17 , 18 , 19 ]. OS triggers membrane and Hb oxidation, clustering, and disruption of band 3-cytoskeleton anchorage, and all these alterations lead to EV formation [ 7 , 17 , 20 , 21 , 22 , 23 ]. All these data indicate that there are various mechanisms of RBC-derived EV formation, however, several questions are still unsolved.…”