Stored red blood cells enhance in vivo migration of dendritic cells by promoting reactive oxygen species-induced cytoskeletal rearrangement

Transfusion ◽  
2019 ◽  
Vol 59 (4) ◽  
pp. 1312-1323
Author(s):  
Man Zhao ◽  
Qianqian Zhou ◽  
Chulin He ◽  
Yulong Zhang ◽  
Zhengjun Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dendritic Cells ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cytoskeletal Rearrangement

scholarly journals Protein-L-isoaspartate O-methyltransferase is required for in vivo control of oxidative damage in red blood cells

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Angelo D’Alessandro ◽  
Ariel Hay ◽  
Monika Dzieciatkowska ◽  
Benjamin C. Brown ◽  
Evan J Morrison ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Metabolic Reprogramming ◽  
Oxygen Species ◽  
Common Amino Acid

Red blood cells have the special challenge of a large amount of reactive oxygen species (from their substantial iron load and Fenton reactions) combined with the inability to synthesize new gene products. Considerable progress has been made in elucidating the multiple pathways by which red blood cells neutralize reactive oxygen species via NADPH driven redox reactions. However, far less is known about how red blood cells repair the inevitable damage that does occur when reactive oxygen species break through anti-oxidant defenses. When structural and functional proteins become oxidized, the only remedy available to red blood cells is direct repair of the damaged molecules, as red blood cells cannot synthesize new proteins. Amongst the most common amino acid targets of oxidative damage is the conversion of asparagine and aspartate side chains into a succinimidyl group through deamidation or dehydration, respectively. Red blood cells express an L-Isoaspartyl methyltransferase (PIMT, gene name PCMT1) that can convert succinimidyl groups back to an aspartate. Herein, we report that deletion of PCMT1 significantly alters red blood cell metabolism in a healthy state, but does not impair the circulatory lifespan of red blood cells. Through a combination of genetic ablation, bone marrow transplantation and oxidant stimulation with phenylhydrazine in vivo or blood storage ex vivo, we use omics approaches to show that, when animals are exposed to oxidative stress, red blood cells from PCMT1 knockout undergo significant metabolic reprogramming and increased hemolysis. This is the first report of an essential role of PCMT1 for normal RBC circulation during oxidative stress.

Hepcidin as a Therapeutic Tool to Limit Iron Overload and Improve Anemia In β-Thalassemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1009-1009 ◽  
Author(s):  
Sara Gardenghi ◽  
Pedro Ramos ◽  
Cindy N. Roy ◽  
Nancy C. Andrews ◽  
Elizabeta Nemeth ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Life Span ◽  
Red Blood Cells ◽  
Iron Content ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Red Cell ◽  
Oxygen Species ◽  
Ineffective Erythropoiesis

Abstract Abstract 1009 The principal regulator of iron homeostasis, the hepatic peptide hepcidin (Hamp), degrades the iron-transport protein ferroportin (Fpn) localized on absorptive enterocytes, hepatocytes and macrophages. Low Hamp expression has been associated with iron overload in patients and mice affected by β-thalassemia intermedia (th3/+). Our hypothesis is that more iron is absorbed than required for erythropoiesis in β-thalassemia. Therefore, we propose that limiting the dietary iron intake of th3/+ mice either by feeding them a low iron diet or increasing their Hamp expression will have a beneficial effect on iron overload with no effects on erythropoiesis. In particular, since Hamp expression is low in β-thalassemia, a moderate increase of Hamp expression should not interfere with erythropoiesis by preventing release of iron from macrophages. However, we predict that very high levels of Hamp expression will limit the recycling of iron from macrophages, thereby exacerbating the anemia. We first analyzed wt and th3/+ mice fed diets containing a physiological amount of iron (35 ppm) or low iron (2.5 ppm) for 1 and 5 months. These mice were then compared to wt and th3/+ mice expressing a transgenic Hamp (THamp and THamp/th3, respectively). In wt mice, the low-iron diet decreased tissue iron levels leading to anemia (Hb: 14.6±0.7 g/dL and 8.6±2.4 g/dL at 1 and 5 months, respectively). In th3/+ mice fed the low-iron diet, the amount of iron in the liver and spleen decreased over time and after 5 months was 10 times lower than at the beginning of treatment. However, in this case the low-iron diet did not worsen the anemia, (Hb: 8.2±1.3 g/dL vs. 7.8±1.8 g/dL at 1 and 5 months, respectively). In the case of THamp and THamp/th3 mice, we stratified those animals whose transgenic Hamp expression was moderate (2-4 higher) or high (>4 times higher) compared to the endogenous Hamp expression in control mice. In THamp animals expressing a moderate level of Hamp, the total iron content of the liver was decreased (65±21 μg vs. 131±31 μg in wt controls) while no significant changes were detected in the spleen. THamp mice also exhibited anemia (Hb: 11.2±1.8 g/dL vs. 13.9±1.1 g/dL at 1 month). The iron content of the liver and spleen was reduced in THamp/th3 (127±86 μg vs. 234±49 μg and 131±88 μg vs. 271±74 μg, respectively, compared to th3/+ controls), while their hematological values were dramatically improved. Splenomegaly was also significantly reduced. Similar findings were observed at 5 months. Looking at animals expressing high levels of transgenic Hamp, both THamp and THamp/th3 mice exhibited vast accumulations of iron in macrophages, profound anemia, reticulocytosis and increased splenomegaly, confirming that high levels of Hamp block iron recycling and are detrimental to erythropoiesis. Interestingly, in THamp/th3 mice expressing a moderate level of Hamp we observed that the increase in hemoglobin levels was associated with increased red cell numbers but reduced mean corpuscular hemoglobin levels. Paradoxically, this could indicate that reduction of the anemia in THamp/th3 mice is mediated by decreased heme synthesis. α-Globin/heme aggregates lead to ineffective erythropoiesis and a limited red cell life span by producing reactive oxygen species and altering the structure of red cell membranes. Compared to th3/+ mice, THamp/th3 mice exhibited reduced heme contents, insoluble membrane-bound α-globins and reactive oxygen species resulting in an increased life span and more normal morphology of their red blood cells. While the number of red blood cells was increased, the number of reticulocytes, and the total number of erythroid precursors in the spleen were reduced. This was associated with a reduction in reactive oxygen species. Cell cycle analysis of the erythroid cells at different stages of differentiation, expression of heme related proteins and synthesis of α- and β-globin chains in THamp/th3 mice is in progress. Overall, this study indicates that use of hepcidin might be effective in reducing iron overload and improving erythropoiesis in β-thalassemia thereby limiting toxicity due to heme not incorporated into the adult hemoglobin tetramer. In conclusion, we believe this study provides the first evidence that hepcidin could be utilized for the treatment of abnormal iron absorption in β-thalassemia and other related disorders, with additional beneficial effects on ineffective erythropoiesis, splenomegaly and anemia. Disclosures: Nemeth: Intrinsic Life Sciences: Employment, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Thalassemic DNA-Containing Red Blood Cells Are under Oxidative Stress

Anemia ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Mutaz Dana ◽  
Eugenia Prus ◽  
Eitan Fibach
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Oxidative Status ◽  
Oxygen Species ◽  
Dna Breakage ◽  
Erythroid Precursors

We studied the nature of enucleated RBCs containing DNA remnants, Howell-Jolly (HJ) RBCs and reticulocytes (retics), that are characteristically present in the circulation of thalassemic patients, especially after splenectomy. Using flow cytometry methodology, we measured oxidative status parameters of these cells in patients withβ-thalassemia. In each patient studied, these cells had higher content of reactive oxygen species and exposed phosphatidylserine compared with their DNA-free counterparts. These results suggest that oxidative stress in thalassemic developing erythroid precursors might, through DNA-breakage, generate HJ-retics and HJ-RBCs and that oxidative stress-induced externalization of phosphatidylserine is involved in the removal of these cells from the circulation by the spleen, a mechanism similar to that of the removal of senescent RBCs.

scholarly journals Hemoglobin polymerization via disulfide bond formation in the hypoxia-tolerant turtle Trachemys scripta: implications for antioxidant defense and O2 transport

2018 ◽  
Vol 314 (1) ◽  
pp. R84-R93 ◽  
Author(s):  
Asbjørn G. Petersen ◽  
Steen V. Petersen ◽  
Sebastian Frische ◽  
Srdja Drakulic ◽  
Monika M. Golas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Disulfide Bonds ◽  
Reactive Oxygen ◽  
Trachemys Scripta ◽  
Freshwater Turtle ◽  
Oxygen Species ◽  
Cell Defense

The ability of many reptilian hemoglobins (Hbs) to form high-molecular weight polymers, albeit known for decades, has not been investigated in detail. Given that turtle Hbs often contain a high number of cysteine (Cys), potentially contributing to the red blood cell defense against reactive oxygen species, we have examined whether polymerization of Hb could occur via intermolecular disulfide bonds in red blood cells of freshwater turtle Trachemys scripta, a species that is highly tolerant of hypoxia and oxidative stress. We find that one of the two Hb isoforms of the hemolysate HbA is prone to polymerization in vitro into linear flexible chains of different size that are visible by electron microscopy but not the HbD isoform. Polymerization of purified HbA is favored by hydrogen peroxide, a main cellular reactive oxygen species and a thiol oxidant, and inhibited by thiol reduction and alkylation, indicating that HbA polymerization is due to disulfide bonds. By using mass spectrometry, we identify Cys5 of the αA-subunit of HbA as specifically responsible for forming disulfide bonds between adjacent HbA tetramers. Polymerization of HbA does not affect oxygen affinity, cooperativity, and sensitivity to the allosteric cofactor ATP, indicating that HbA is still fully functional. Polymers also form in T. scripta blood after exposure to anoxia but not normoxia, indicating that they are of physiological relevance. Taken together, these results show that HbA polymers may form during oxidative stress and that Cys5αA of HbA is a key element of the antioxidant capacity of turtle red blood cells.

scholarly journals Involvement of Calcium, Reactive Oxygen Species, and ATP in Hexavalent Chromium-Induced Damage in Red Blood Cells

2014 ◽  
Vol 34 (5) ◽  
pp. 1780-1791 ◽  
Author(s):  
Rong Zhang ◽  
Yang Xiang ◽  
Qian Ran ◽  
Xiaojun Deng ◽  
Yanni Xiao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Red Blood Cells ◽  
Hexavalent Chromium ◽  
Blood Cells ◽  
Reactive Oxygen ◽  
Oxygen Species
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