a(MESH:"Cell-Derived Microparticles")
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
MPs are small membrane-derived vesicles that are shed upon activation, inflammation, or cell death/damage. PubMed:29929138
Surface accumulation of MAC may be at least partially responsible for the activated platelet phenotype seen in patients with primary Cys89Tyr CD59 mutation, as manifested both by increased CD62P expression and monocyte-platelet aggregates. PubMed:29929138
Activation, aging, and apoptosis of various cells, including RBCs, are accompanied by formation of microscopic extracellular membranous structures named microvesicles or microparticles (MPs). PubMed:28458720
Interestingly, a recent study demonstrated that, in severe hemolytic disease (sickle cell anemia), at least one third of plasma heme was associated with membrane vesicle structures (microparticles) that were generated from erythrocytes during hemolysis [24]. PubMed:26875449
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
We have assessed the presence of MPs in four patients with primary Cys89Tyr mutation in CD59 and two PNH patients, as well as in four healthy donors. PubMed:29929138
In summary, patients with primary Cys89Tyr mutation in CD59 showed about 9–10-fold increase in the number of MPs compared to controls and slightly but significantly increased numbers when com pared to PNH patients. The origin of MPs was primarily RBCs and to a much lesser extent platelets and neutrophils. PubMed:29929138
Endothelial injury may also be related to Free hemoglobin and its breakdown oxidative product heme, and MPs, which mediates direct proinflammatory, proliferative, and pro-oxidant effects on endothelial cells [22–24] both in PNH and congenital CD59 deficiency, but may be more pronounced in congenital CD59 deficiency and perhaps even more in the brain due to loss of CD59 in the endothelium of these patients. PubMed:29929138
We have assessed the presence of MPs in four patients with primary Cys89Tyr mutation in CD59 and two PNH patients, as well as in four healthy donors. PubMed:29929138
In summary, patients with primary Cys89Tyr mutation in CD59 showed about 9–10-fold increase in the number of MPs compared to controls and slightly but significantly increased numbers when com pared to PNH patients. The origin of MPs was primarily RBCs and to a much lesser extent platelets and neutrophils. PubMed:29929138
Interestingly, a recent study demonstrated that, in severe hemolytic disease (sickle cell anemia), at least one third of plasma heme was associated with membrane vesicle structures (microparticles) that were generated from erythrocytes during hemolysis [24]. PubMed:26875449
Third, hemolysis results in a massive release of procoagulant RBC-derived MPs [66]. PubMed:28458720
MPs are small membrane-derived vesicles that are shed upon activation, inflammation, or cell death/damage. PubMed:29929138
In this work, we were able to document a significant increase in RBCderived MPs, and a lesser increase in PMN- and platelet-derived MPs, in these patient s. This increase in MPs may lead to the thrombophilic state [15]. PubMed:29929138
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
Formation of RBC-derived MPs is typical during the ex vivo storage of whole blood [52] and accumulation of MPs is thought to be responsible for an increased incidence of deep vein thrombosis after transfusion of “old” red cells [53]. PubMed:28458720
Irrespective of their source, elevated plasma levels of MPs are associated with a reduced clotting time and a dose- and time-dependent increase in thrombin generation, suggesting that the MPs enhance hypercoagulability. PubMed:28458720
Irrespective of their source, elevated plasma levels of MPs are associated with a reduced clotting time and a dose- and time-dependent increase in thrombin generation, suggesting that the MPs enhance hypercoagulability. PubMed:28458720
The circulating MPs can internalize free heme and transfer it to vascular endothelium, promoting vaso-occlusion, or amplify systemic inflammation via thrombin mediated activation of the complement system [57]. PubMed:28458720
The circulating MPs can internalize free heme and transfer it to vascular endothelium, promoting vaso-occlusion, or amplify systemic inflammation via thrombin mediated activation of the complement system [57]. PubMed:28458720
Endothelial injury may also be related to Free hemoglobin and its breakdown oxidative product heme, and MPs, which mediates direct proinflammatory, proliferative, and pro-oxidant effects on endothelial cells [22–24] both in PNH and congenital CD59 deficiency, but may be more pronounced in congenital CD59 deficiency and perhaps even more in the brain due to loss of CD59 in the endothelium of these patients. PubMed:29929138
Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24]. PubMed:29929138
Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24]. PubMed:29929138
Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24]. PubMed:29929138
Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24]. PubMed:29929138
Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24]. PubMed:29929138
In this work, we were able to document a significant increase in RBCderived MPs, and a lesser increase in PMN- and platelet-derived MPs, in these patient s. This increase in MPs may lead to the thrombophilic state [15]. PubMed:29929138
Surface accumulation of MAC may be at least partially responsible for the activated platelet phenotype seen in patients with primary Cys89Tyr CD59 mutation, as manifested both by increased CD62P expression and monocyte-platelet aggregates. PubMed:29929138
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