Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport

References

• Bianconi E , Piovesan A , Facchin F , et al. An estimation of the number of cells in the human body. Ann. Hum. Biol. 2013;40:463–471.
   PubMed Web of Science ®Google Scholar
• Sender R , Fuchs S , Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14:e1002533.
   PubMed Web of Science ®Google Scholar
• Bryk AH , Wiśniewski JR. Quantitative analysis of human red blood cell proteome. J Proteome Res. 2017;16:2752–2761.
   PubMedGoogle Scholar
• D’Alessandro A , Dzieciatkowska M , Nemkov T , et al. Red blood cell proteomics update: is there more to discover?. Blood Transfus. 2017;15:182–187.
   PubMed Web of Science ®Google Scholar
• Chu TTT , Sinha A , Malleret B , et al. Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br. J. Haematol.. 2018;180:118–133.
   PubMed Web of Science ®Google Scholar
• Wilson MC , Trakarnsanga K , Heesom KJ , et al. Comparison of the proteome of adult and cord erythroid cells, and changes in the proteome following reticulocyte maturation. Mol Cell Proteomics MCP. 2016;15:1938–1946.
   PubMed Web of Science ®Google Scholar
• Jensen FB. Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport. Acta Physiol. Scand. 2004;182:215–227.
   PubMedGoogle Scholar
• Hemingway A , Hemingway CJ , Roughton FJ . The rate of the chloride shift of respiration studied with a rapid filtration method. Respir. Physiol.. 1970;10:1–9.
   PubMedGoogle Scholar
• Taylor AT . High-altitude illnesses: physiology, risk factors, prevention, and treatment. Rambam Maimonides Med J Rambam Maimonides Med J. 2011;2(1):e0022.
   PubMedGoogle Scholar
• Nemkov T , Hansen KC , Dumont LJ , et al. Metabolomics in transfusion medicine. Transfusion. 2016;56:980–993.
   PubMed Web of Science ®Google Scholar
• Tsai AG , Hofmann A , Cabrales P , et al. Perfusion vs. oxygen delivery in transfusion with “fresh” and “old” red blood cells: the experimental evidence.. Transfus Apher Sci Off J World Apher Assoc Off J Eur Soc Haemapheresis. 2010;43:69–78.
   PubMed Web of Science ®Google Scholar
• D’Alessandro A , Reisz JA , Culp-Hill R , et al. Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells. Transfusion; 2018;58(8):1992-2002.
   Google Scholar
• Wan J , Ristenpart WD , Stone HA . Dynamics of shear-induced ATP release from red blood cells. Proc Natl Acad Sci. 2008;105:16432–16437.
   PubMed Web of Science ®Google Scholar
• Ralevic V , Dunn WR . Purinergic transmission in blood vessels. Auton Neurosci Basic Clin. 2015;191:48–66.
   PubMed Web of Science ®Google Scholar
• Liu H , Zhang Y , Wu H , et al. Beneficial role of erythrocyte adenosine A2B receptor-mediated AMP-activated protein kinase activation in high-altitude hypoxia. Circulation. 2016;134:405–421.
   PubMed Web of Science ®Google Scholar
• Sun K , Zhang Y , D’Alessandro A , et al. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun. 2016;7:12086.
   PubMed Web of Science ®Google Scholar
• Sun K , Liu H , Song A , et al. Erythrocyte purinergic signaling components underlie hypoxia adaptation. J. Appl. Physiol. Bethesda Md. 1985;2017(123):951–956.
   Google Scholar
• Song A , Zhang Y , Han L , et al. Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent. Nat Commun. 2017;8:14108.
   PubMed Web of Science ®Google Scholar
• Carelli-Alinovi C , Ficarra S , Russo AM , et al. Involvement of acetylcholinesterase and protein kinase C in the protective effect of caffeine against β-amyloid-induced alterations in red blood cells. Biochimie. 2016;121:52–59.
   PubMed Web of Science ®Google Scholar
• D’Alessandro A , Nemkov T , Sun K , et al. AltitudeOmics: red blood cell metabolic adaptation to high altitude hypoxia. J Proteome Res. 2016;15:3883–3895.
   PubMed Web of Science ®Google Scholar
• Chu H , Breite A , Ciraolo P , et al. Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: implications for O2 regulation of erythrocyte properties. Blood. 2008;111:932–938.
   PubMed Web of Science ®Google Scholar
• Chu H , McKenna MM , Krump NA , et al. Reversible binding of hemoglobin to band 3 constitutes the molecular switch that mediates O2 regulation of erythrocyte properties. Blood. 2016;128:2708–2716.
   PubMed Web of Science ®Google Scholar
• Harrison ML , Rathinavelu P , Arese P , et al. Role of band 3 tyrosine phosphorylation in the regulation of erythrocyte glycolysis. J Biol Chem. 1991;266:4106–4111.
   PubMed Web of Science ®Google Scholar
• Campanella ME , Chu H , Wandersee NJ , et al. Characterization of glycolytic enzyme interactions with murine erythrocyte membranes in wild-type and membrane protein knockout mice. Blood. 2008;112:3900–3906.
   PubMed Web of Science ®Google Scholar
• Chu H , Low PS . Mapping of glycolytic enzyme-binding sites on human erythrocyte band 3. Biochem J. 2006;400:143–151.
   PubMed Web of Science ®Google Scholar
• Low PS , Rathinavelu P , Harrison ML . Regulation of glycolysis via reversible enzyme binding to the membrane protein, band 3. J Biol Chem. 1993;268:14627–14631.
   PubMed Web of Science ®Google Scholar
• Gladwin MT , Lancaster JR , Freeman BA , et al. Nitric oxide’s reactions with hemoglobin: a view through the SNO-storm. Nat. Med.. 2003;9:496–500.
   PubMed Web of Science ®Google Scholar
• Gladwin MT , Shelhamer JH , Schechter AN , et al. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc. Natl. Acad. Sci. U. S. A. 2000;97:11482–11487.
   PubMed Web of Science ®Google Scholar
• Cortese-Krott MM , Kelm M . Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function?. Redox Biol. 2014;2:251–258.
   PubMed Web of Science ®Google Scholar
• Diesen DL , Hess DT , Stamler JS . Hypoxic vasodilation by red blood cells. Circ Res. 2008;103:545–553.
   PubMed Web of Science ®Google Scholar
• Castagnola M , Messana I , Sanna MT , et al. Oxygen-linked modulation of erythrocyte metabolism: state of the art. Blood Transfus. 2010;8:s53–s58.
   PubMed Web of Science ®Google Scholar
• Kuhn V , Diederich L , Keller TCS , et al. Red blood cell function and dysfunction: redox regulation, nitric oxide metabolism, anemia. Antioxid. Redox Signal.. 2017;26:718–742.
   PubMed Web of Science ®Google Scholar
• Reisz JA , Wither MJ , Dzieciatkowska M , et al. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells. Blood. 2016;128:e32–42.
   PubMed Web of Science ®Google Scholar
• Hildebrandt T , Knuesting J , Berndt C , et al. Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub? Biol. Chem. 2015;396:523–537.
   Web of Science ®Google Scholar
• D’Alessandro A , Nemkov T , Yoshida T , et al. Citrate metabolism in red blood cells stored in additive solution-3. Transfusion. 2017;57:325–336.
   PubMed Web of Science ®Google Scholar
• Brooks GA. The Science and . Translation of lactate shuttle theory. Cell Metab. 2018;27:757–785.
   PubMed Web of Science ®Google Scholar
• San-Millán I , Brooks GA . Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect. Carcinogenesis. 2017;38:119–133.
   PubMed Web of Science ®Google Scholar
• J C H-A , Enríquez-Gasca MDR , Hernández-Ortiz M , et al. Proteomic patterns of cervical cancer cell lines, a network perspective. BMC Syst. Biol. 2011;5:110.
   PubMed Web of Science ®Google Scholar
• D’Alessandro A , Righetti PG , Zolla L . The red blood cell proteome and interactome: an update. J Proteome Res. 2010;9:144–163.
   PubMed Web of Science ®Google Scholar
• Bosman GJCGM . The proteome of the red blood cell: an auspicious source of new insights into membrane-centered regulation of homeostasis. Proteomes. 2016 Nov 25;4(4). pii: E35. doi: 10.3390/proteomes4040035.
   Google Scholar
• Nathan DG . Amino acid uptake in erythropoiesis. Sci. Signal.. 2015;8:fs9.
   PubMed Web of Science ®Google Scholar
• Reisz JA , Slaughter AL , Culp-Hill R , et al. Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats. Blood Adv. 2017;1:1296–1305.
   PubMed Web of Science ®Google Scholar
• Kendrick AA , Schafer J , Dzieciatkowska M , et al. CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming. Oncotarget. 2016;8:6742–6762.
   Google Scholar
• Thomas SLY , Bouyer G , Cueff A , et al. Ion channels in human red blood cell membrane: actors or relics? Blood cells. Mol Dis. 2011;46:261–265.
   Web of Science ®Google Scholar
• Kuchel PW , Benga G . Why does the mammalian red blood cell have aquaporins?. Biosystems. 2005;82:189–196.
   PubMed Web of Science ®Google Scholar
• Benga G , Banner M , Wrigglesworth JM . Quantitation of the water channel protein aquaporin (CHIP28) from red blood cell membranes by densitometry of silver stained polyacrylamide gels. Electrophoresis. 1996;17:715–719.
   PubMed Web of Science ®Google Scholar
• Roudier N , Verbavatz JM , Maurel C , et al. Evidence for the presence of aquaporin-3 in human red blood cells. J Biol Chem. 1998;273:8407–8412.
   PubMed Web of Science ®Google Scholar
• Kingsley PD , Greenfest-Allen E , Frame JM , et al. Ontogeny of erythroid gene expression. Blood. 2013;121:e5–e13.
   PubMed Web of Science ®Google Scholar
• Deth R , Muratore C , Benzecry J , et al. How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology. 2008;29:190–201.
   PubMed Web of Science ®Google Scholar
• Makhro A , Hänggi P , Goede JS , et al. N-methyl-D-aspartate receptors in human erythroid precursor cells and in circulating red blood cells contribute to the intracellular calcium regulation. Am J Physiol Cell Physiol. 2013;305:C1123–1138.
   PubMed Web of Science ®Google Scholar
• Makhro A , Kaestner L , Bogdanova A . NMDA receptor activity in circulating red blood cells: methods of detection. Methods Mol. Biol. Clifton NJ.. 2017;1677:265–282.
   PubMedGoogle Scholar
• Amireault P , Bayard E , Launay J-M , et al. serotonin is a key factor for mouse red blood cell survival. PLoS ONE PLoS One. 2013;8(12):e83010.
   PubMed Web of Science ®Google Scholar
• Tesoriere L , D’Arpa D , Conti S , et al. Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity. J Pineal Res. 1999;27:95–105.
   PubMed Web of Science ®Google Scholar
• Hartai Z , Klivenyi P , Janaky T , et al. Kynurenine metabolism in plasma and in red blood cells in Parkinson’s disease. J Neurol Sci. 2005;239:31–35.
   PubMed Web of Science ®Google Scholar
• D’Amato NC , Rogers TJ , Gordon MA , et al. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer. Cancer Res. 2015;75:4651–4664.
   PubMed Web of Science ®Google Scholar
• Culp-Hill R , Zheng C , Reisz JA , et al. Red blood cell metabolism in Down syndrome: hints on metabolic derangements in aging. Blood Adv. 2017;1:2776–2780.
   PubMed Web of Science ®Google Scholar
• Giil LM , Ø M , Refsum H , et al. Kynurenine pathway metabolites in Alzheimer’s disease. J. Alzheimers Dis. JAD. 2017;60:495–504.
   PubMed Web of Science ®Google Scholar
• Lim CK , Fernández-Gomez FJ , Braidy N , et al. Involvement of the kynurenine pathway in the pathogenesis of Parkinson’s disease. Prog Neurobiol. 2017;155:76–95.
   PubMed Web of Science ®Google Scholar
• Tang LC . Identification and characterization of human erythrocyte muscarinic receptors. Gen. Pharmacol.. 1986;17:281–285.
   PubMedGoogle Scholar
• Kim ER , Fan S , Akhmedov D , et al. Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply. JCI Insight. 2017;14(2):pii: 93367.
   Google Scholar
• Azoui R , Cuche JL , Renaud JF , et al. A dopamine transporter in human erythrocytes: modulation by insulin. Exp Physiol. 1996;81:421–434.
   PubMed Web of Science ®Google Scholar
• Buttarelli FR , Fanciulli A , Pellicano C , et al. The dopaminergic system in peripheral blood lymphocytes: from physiology to pharmacology and potential applications to neuropsychiatric disorders. Curr. Neuropharmacol. 2011;9:278–288.
   PubMed Web of Science ®Google Scholar
• Kosower EM . A partial structure for the gamma-aminobutyric acid (GABAA) receptor is derived from the model for the nicotinic acetylcholine receptor. The Anion-Exchange Protein of Cell Membranes Is Related to the GABAA Receptor. FEBS Lett. 1988;231:5–10.
   Google Scholar
• Bachman E , Travison TG , Basaria S , et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J. Gerontol. A. Biol. Sci. Med. Sci. 2014;69:725–735.
   PubMed Web of Science ®Google Scholar
• Kanias T , Sinchar D , Osei-Hwedieh D , et al. Testosterone-dependent sex differences in red blood cell hemolysis in storage, stress, and disease. Transfusion. 2016;56:2571–2583.
   PubMed Web of Science ®Google Scholar
• Yin J , Guo Y-M , Chen P , et al. Testosterone regulates the expression and functional activity of sphingosine-1-phosphate receptors in the rat corpus cavernosum. J. Cell. Mol. Med. 2018;22:1507–1516.
   PubMed Web of Science ®Google Scholar
• Nemkov T , Sun K , Reisz JA , et al. Metabolism of citrate and other carboxylic acids in erythrocytes as a function of oxygen saturation and refrigerated storage. Front. Med. 2017;4:175.
   Web of Science ®Google Scholar
• Ó R , Óe S , Magnusdottir M , et al. Metabolomics comparison of red cells stored in four additive solutions reveals differences in citrate anticoagulant permeability and metabolism. Vox Sang. 2017;112:326–335.
   PubMed Web of Science ®Google Scholar
• Nemkov T , Sun K , Reisz JA , et al. Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage. Haematologica. 2018;103:361–372.
   PubMed Web of Science ®Google Scholar
• DʼAlessandro A , Moore HB , Moore EE , et al. Plasma succinate is a predictor of mortality in critically injured patients. J Trauma Acute Care Surg. 2017;83:491–495.
   PubMed Web of Science ®Google Scholar
• Jiang S , Yan W . Succinate in the cancer-immune cycle. Cancer Lett. 2017;390:45–47.
   PubMed Web of Science ®Google Scholar
• Laj O , Kishton RJ , Rathmell J . A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016;16:553–565.
   PubMed Web of Science ®Google Scholar
• Brand A , Singer K , Koehl GE , et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016;24:657–671.
   PubMed Web of Science ®Google Scholar
• Scott KEN , Cleveland JL . Lactate wreaks havoc on tumor-infiltrating T and NK cells. Cell Metab. 2016;24:649–650.
   PubMed Web of Science ®Google Scholar
• Grist JT , Jarvis LB , Georgieva Z , et al. Extracellular lactate: a novel measure of t cell proliferation. J Immunol Baltim Md. 1950;2018(200):1220–1226.
   Google Scholar
• Bishlawy IM . Red blood cells, hemoglobin and the immune system. Med. Hypotheses.. 1999;53:345–346.
   PubMed Web of Science ®Google Scholar
• Buttari B , Profumo E , Riganò R . Crosstalk between red blood cells and the immune system and its impact on atherosclerosis. Biomed Res Int. 2015;2015:616834.
   PubMed Web of Science ®Google Scholar
• Mondanelli G , Bianchi R , Pallotta MT , et al. A relay pathway between arginine and tryptophan metabolism confers immunosuppressive properties on dendritic cells. Immunity. 2017;46:233–244.
   PubMed Web of Science ®Google Scholar
• Gomes-Trolin C , Nygren I , Aquilonius S-M , et al. Increased red blood cell polyamines in ALS and Parkinson’s disease. Exp Neurol. 2002;177:515–520.
   PubMed Web of Science ®Google Scholar
• Loguercio C , Nardi G , Argenzio F , et al. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol Alcohol. Oxf. Oxfs.. 1994;29:597–604.
   PubMed Web of Science ®Google Scholar
• Hoyer J , Oliveira J , Baumann N , et al. A reassessment of the red blood cell folate assay. Blood. 2010;116:3209.
   Web of Science ®Google Scholar
• Ingrosso D , D’angelo S . di Carlo E, et al. Increased Methyl Esterification of Altered Aspartyl Residues in Erythrocyte Membrane Proteins in Response to Oxidative Stress. Eur. J. Biochem.. 2000;267:4397–4405.
   Google Scholar
• Galletti P , Ingrosso D , Nappi A , et al. Increased methyl esterification of membrane proteins in aged red-blood cells. Preferential Esterification Ankyrin Band-4.1 Cytoskeletal Proteins Eur J Biochem. 1983;135:25–31.
   Google Scholar
• Youssef LA , Rebbaa A , Pampou S , et al. Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion. Blood. 2018.
   PubMed Web of Science ®Google Scholar
• Rapido F , Brittenham GM , Bandyopadhyay S , et al. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest. 2017;127:375–382.
   PubMed Web of Science ®Google Scholar
• Hod EA , Brittenham GM , Billote GB , et al. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood. 2011;118:6675–6682.
   PubMed Web of Science ®Google Scholar
• Hod EA , Zhang N , Sokol SA , et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood. 2010;115:4284–4292.
   PubMed Web of Science ®Google Scholar
• Korolnek T , Hamza I . Macrophages and iron trafficking at the birth and death of red cells. Blood. 2015;125:2893–2897.
   PubMed Web of Science ®Google Scholar
• Alexeev EE , He X , Slupsky CM , et al. Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups. PLoS ONE [Internet]. 2017 [cited 2018 Sep 12 ];12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491036/.
   Google Scholar
• Cherayil BJ , Ellenbogen S , Shanmugam NN . Iron and intestinal immunity. Curr Opin Gastroenterol. 2011;27:523–528.
   PubMed Web of Science ®Google Scholar
• Manzo VE , Bhatt AS . The human microbiome in hematopoiesis and hematologic disorders. Blood. 2015;126:311–318.
   PubMed Web of Science ®Google Scholar
• Muckenthaler MU , Rivella S , Hentze MW , et al. A red carpet for iron metabolism. Cell. 2017;168:344–361.
   PubMed Web of Science ®Google Scholar
• El Kasmi KC , Vue PM , Anderson AL , et al. Macrophage-derived IL-1β/NF-κB signaling mediates parenteral nutrition-associated cholestasis. Nat Commun. 2018;9:1393.
   PubMed Web of Science ®Google Scholar
• Nakano T , Wada Y , Matsumura S . Membrane lipid components associated with increased filterability of erythrocytes from long-distance runners. Clin. Hemorheol. Microcirc.. 2001;24:85–92.
   PubMed Web of Science ®Google Scholar
• Dougherty RM , Galli C , Ferro-Luzzi A , et al. Lipid and phospholipid fatty acid composition of plasma, red blood cells, and platelets and how they are affected by dietary lipids: a study of normal subjects from Italy, Finland, and the USA. Am. J. Clin. Nutr.. 1987;45:443–455.
   PubMed Web of Science ®Google Scholar
• Unruh D , Srinivasan R , Benson T , et al. red blood cell dysfunction induced by high-fat diet. Circulation. 2015;132:1898–1908.
   PubMed Web of Science ®Google Scholar
• Fu X , Felcyn JR , Odem-Davis K , et al. Bioactive lipids accumulate in stored red blood cells despite leukoreduction: a targeted metabolomics study. Transfusion. 2016;56:2560–2570.
   PubMed Web of Science ®Google Scholar
• de Wolski K , Fu X , Dumont LJ , et al. Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells. Haematologica. 2016;101:578–586.
   PubMed Web of Science ®Google Scholar
• Pandey KB , Rizvi SI . Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid. Med. Cell. Longev.. 2010;3:2–12.
   PubMed Web of Science ®Google Scholar
• Wu H , Bogdanov M , Zhang Y , et al. Hypoxia-mediated impaired erythrocyte Lands’ Cycle is pathogenic for sickle cell disease. Sci. Rep.. 2016;6:29637.
   PubMed Web of Science ®Google Scholar
• Sphingosine CH . 1-phosphate and immune regulation: trafficking and beyond. Trends Pharmacol Sci. 2011;32:16–24.
   PubMed Web of Science ®Google Scholar
• Mühle C , Reichel M , Gulbins E , et al. Sphingolipids in psychiatric disorders and pain syndromes. Handb Exp Pharmacol. 2013;(216):431–456.
   PubMedGoogle Scholar
• Yerrabothala S , Tsongalis GJ , Fu X , et al. Correlation between red blood cell survival and cytochrome p450 1a2 enzyme activity. Blood. 2013;122:3658.
   Web of Science ®Google Scholar
• Devinsky O , Cilio MR , Cross H , et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791–802.
   PubMed Web of Science ®Google Scholar
• Cossum PA . Role of the red blood cell in drug metabolism. Biopharm. Drug Dispos.. 1988;9:321–336.
   PubMed Web of Science ®Google Scholar
• Horita A . The antagonism of monoamine oxidase (mao) inhibitors by the red blood cell and its constituents. Toxicol. Appl. Pharmacol.. 1965;7:97–103.
   PubMed Web of Science ®Google Scholar
• Zimring JC , Smith N , Stowell SR , et al. Strain-specific red blood cell storage, metabolism, and eicosanoid generation in a mouse model. Transfusion. 2014;54:137–148.
   PubMed Web of Science ®Google Scholar
• Hay A , Howie HL , Waterman HR , et al. Murine red blood cells from genetically distinct donors cross-regulate when stored together. Transfusion. 2017;57:2657–2664.
   PubMed Web of Science ®Google Scholar
• Tzounakas VL , Kriebardis AG , Georgatzakou HT , et al. Glucose 6-phosphate dehydrogenase deficient subjects may be better “storers” than donors of red blood cells. Free Radic. Biol. Med.. 2016;96:152–165.
   PubMed Web of Science ®Google Scholar
• Tzounakas VL , Georgatzakou HT , Kriebardis AG , et al. Uric acid variation among regular blood donors is indicative of red blood cell susceptibility to storage lesion markers: a new hypothesis tested. Transfusion. 2015;55:2659–2671.
   PubMed Web of Science ®Google Scholar
• Wang S , Dale GL , Song P , et al. AMPKα1 deletion shortens erythrocyte life span in mice. J Biol Chem. 2010;285:19976–19985.
   PubMed Web of Science ®Google Scholar
• Hortle E , Nijagal B , Bauer DC , et al. Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice. Blood. 2016;128:1290–1301.
   PubMed Web of Science ®Google Scholar
• Barzilai N , Crandall JP , Kritchevsky SB , et al. Metformin as a tool to target aging. Cell Metab. 2016;23:1060–1065.
   PubMed Web of Science ®Google Scholar
• Cavalli G , Justice JN , Boyle KE , et al. Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance. Proc. Natl. Acad. Sci. U. S. A.. 2017;114:2313–2318.
   PubMed Web of Science ®Google Scholar
• Kaestner L , Minetti G . The potential of erythrocytes as cellular aging models. Cell Death Differ. 2017;24:1475–1477.
   PubMed Web of Science ®Google Scholar
• J-P C , Desprez P-Y , Krtolica A , et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol.. 2010;5:99–118.
   PubMed Web of Science ®Google Scholar
• Lang F , Gulbins E , Lerche H , et al. Eryptosis, a window to systemic disease. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol.. 2008;22:373–380.
   PubMed Web of Science ®Google Scholar
• Pretorius E . Plooy JN du, Bester J. Comprehensive Review Eryptosis Cell Physiol Biochem. 2016;39:1977–2000.
   PubMedGoogle Scholar
• Harris R . Contribution made by parabiosis to the understanding of energy balance regulation. Biochim. Biophys. Acta.. 2013;1832:1449–1455.
   PubMed Web of Science ®Google Scholar
• Villeda SA , Plambeck KE , Middeldorp J , et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med.. 2014;20:659–663.
   PubMed Web of Science ®Google Scholar
• Castellano JM , Mosher KI , Abbey RJ , et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017;544:488–492.
   PubMed Web of Science ®Google Scholar
• Fredriksson K , Liu XD , Lundahl J , et al. Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol.. 2006;290:L326–333.
   PubMed Web of Science ®Google Scholar
• Kannan M , Atreya C . Differential profiling of human red blood cells during storage for 52 selected microRNAs. Transfusion. 2010;50:1581–1588.
   PubMed Web of Science ®Google Scholar
• Umemura T , Tanaka Y , Fujisaki M , et al. MicroRNA-Ago2 complex in mature human red blood cells. Blood. 2009;114:4042.
   Web of Science ®Google Scholar
• Wang Z , Xi J , Hao X , et al. Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum. Emerg Microbes Infect. 2017;6:e75.
   PubMed Web of Science ®Google Scholar
• Yi T , Li J , Chen H , et al. Splenic dendritic cells survey red blood cells for missing self-cd47 to trigger adaptive immune responses. Immunity. 2015;43:764–775.
   PubMed Web of Science ®Google Scholar
• Nguyen DB , Wagner-Britz L , Maia S , et al. Regulation of phosphatidylserine exposure in red blood cells. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol.. 2011;28:847–856.
   PubMed Web of Science ®Google Scholar
• Wagner GM , Chiu DT , Yee MC , et al. Red cell vesiculation–a common membrane physiologic event. J. Lab. Clin. Med.. 1986;108:315–324.
   PubMed Web of Science ®Google Scholar
• Harisa GI , Badran MM , Alanazi FK . Erythrocyte nanovesicles: biogenesis, biological roles and therapeutic approach: erythrocyte nanovesicles. Saudi Pharm J SPJ Off Publ Saudi Pharm Soc. 2017;25:8–17.
   PubMed Web of Science ®Google Scholar
• Usman WM , Pham TC , Kwok YY , et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun. 2018;9:2359.
   PubMed Web of Science ®Google Scholar
• Zolla L , Lupidi G , Marcheggiani M , et al. Red blood cells as carriers for delivering of proteins. Ann Ist Super Sanita. 1991;27:97–103.
   PubMedGoogle Scholar
• Reisz JA , Slaughter AL , Culp-Hill R , et al. Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats. Blood Adv. 2017;1:1296–1305.
   PubMed Web of Science ®Google Scholar
• Nemkov T , Hansen KC , D’Alessandro A . A three-minute method for high-throughput quantitative metabolomics and quantitative tracing experiments of central carbon and nitrogen pathways. Rapid Commun Mass Spectrom RCM. 2017;31:663–673.
   PubMed Web of Science ®Google Scholar
• D’Alessandro A , Giardina B , Gevi F . Clinical metabolomics: the next stage of clinical biochemistry. Blood Transfus. 2012;10: s19–s24. et al.
   PubMed Web of Science ®Google Scholar