Abstract
The average life cycle of a human RBC is approximately 120 days. Generally, by this point, the cell is worn out and damaged. RBCs pass through both the spleen and liver, where specialised immune cells called macrophages are found. Macrophages recognise when an RBC is spent, and undergo a process called phagocytosis where they digest the cell. In this process, the iron in haemoglobin is recycled for use in new blood cells and the hem molecule is degraded, conjugated to bilirubin, and eliminated from the body. All the other cellular proteins are either recycled or eliminated. Historically, this process was thought to occur exclusively in the spleen, but recent studies have shown that it occurs in the bone marrow. The RBC has been analysed from many perspectives: cytological, haematological, and immunological, as well as from the focus of molecular biology, biophysics, and mathematics. Here we analyse how are red blood cells born and how they live and die in a brief overview of the whole process with special mention of the morphological aspects from bone marrow and spleen provided by transmission and scanning electron microscopy.
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Taken from J. Quigley JG, Means RT, Glader B. Wintrobe’s Clinical Hematology (13th Ed).2014






References
Vives Corrons JL (2019) The rare anaemias. Chapter of The Rare Diseases. Intechopen. https://doi.org/10.5772/intechopen.86986
Berga L, Feliu E, Ferran MJ (1987) Rozman C (1987) Contribution of scanning electron microscopy to the structural study of human bone marrow. Sangre 27:3939
Quigley JG, Means RT, Glader B (2014) The birth, life, and death of red blood cells: erythropoiesis, the mature red blood cell, and cell destruction. In: Greer JP, Arber DA, Glader B, List AF, Means RT Jr, Paraskevas F, Foerster J (eds) Wintrobe’s clinical hematology, 13th edn. Lippincott Williams & Wilkins, Philadelphia, pp 83–124
Yoshida H, Kawane K, Koike M, Mori Y, Uchiyama Y, Nagata S (2005) Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437:754
Liang R, Ghaffari S (2016) Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol 174:661–673
Weiss L (1965) The structure of bone marrow: functional interrelationships of vascular and hemopoietic compartments in experimental hemolytic anemia: an electron microscopic study. J Morph 117:467
De Brulyin PP, Michelson HS, Thomas TB (1971) The migration of blood cells of the bone marrow through the sinusoidal wall. J Morphol. 133:417
Berga L, Vives Corrons JL, Feliu E, Woessner S, Rozman C (1983) Hemorheology Theoretical Basis and Clinical Applications. Salvat Editores, Barcelona
Lux S (2016) Anatomy of the red blood cell membrane skeleton: unanswered questions. Blood 12:187
Mebius RE, Kraal G (2005) (2005) Structure and function of the spleen. Nat Rev Immunol 5:606
Pivkin IV, Peng Z, Karniadakis GE, Buffet PA, Dao M, Suresh S (2016) Biomechanics of red blood cells in human spleen and consequences for physiology and disease. Proc Natl Acad Sci U S A 113:7804
Suresh S (2006) Mechanical response of human red blood cells in health and disease: some structure-property-function relationships. J Mater Res 21:1871
Berga L (1985) Spleen and hemolysis. Medicina Clínica (Barcelona) 85:273
Brovelli A, Minetti G (2003) Red cell ageing. In: Bernhardt I, Ellory JC (eds) Red cell membrane transport in health and disease. Springer, Berlin. https://doi.org/10.1007/978-3-662-05181-8_29
Franco RS (2009) The measurement and importance of red cell survival. Am J Hematol 2009(84):109
Groner W, Mohandas N, Bessis M (1980) New optical technique for measuring erythrocyte deformability with the ektacytometer. Clin Chem 26:1435
Lazarova E, Gulbis B, Oirschot BV, van Wijk R (2017) Next-generation osmotic gradient ektacytometry for the diagnosis of hereditary spherocytosis: interlaboratory method validation and experience. Clin Chem Lab Med 55:394
King MJ, Behrens J, Rogers C, Flynn C, Greenwood D, Chamberset, (2000) Rapid flow cytometric test for the diagnosis of membrane cytoskeleton-associated haemolytic anaemia. Br J Haematol 111:924
Merola F, Barroso A, Miccio L, Memmolo P, Mugnano M, Ferraro P, Denz C (2017) Biolens behavior of RBCs under optically-induced mechanical stress. Cytometry A 91:527
Rico LG, Juncà J, Ward MD, Bradford JA, Bardina J, Petriz J (2018) Acoustophoretic orientation of red blood cells for diagnosis of red cell health and pathology. Sci Rep 8:15705
Bernhard I, Nguyen DB, Wesseling MC, Kaestner L (2020) Intracellular Ca 2+ concentration and phosphatidylserine exposure in healthy human erythrocytes in dependence on in vivo cell age. Front Physiol 10(10):1629
Palis J, Segel GB (1998) Developmental biology of erythropoiesis. Blood Rev 12:106
Bosman GJCGM, Lasonder E, Groenen-Döpp YAM, Willekens FLA, Werre JM, Novotý VMJ (2010) Comparative proteomics of erythrocyte aging in vivo and in vitro. J Proteom 73:396
Freikman I, Fibach E (2011) Distribution and shedding of the membrane phosphatidylserine during maturation and aging of erythroid cells. Biochim Biophys Acta 1808:2773
Fernandez Arias C, Fernandez Arias C (2017) How to do red blood cells know when to die? R Soc Open Sci. 4:160850
Song J, Yoon D, Christensen RD, Horvathova M, Thiagarajan P, Prchal JT (2015) HIF-mediated increased ROS from reduced mitophagy and decreased catalase causes neocytolysis. J Mol Med 93:857
Acknowledgements
We are indebted to the European Commission for the Equality Plus (Erasmus +) Grant (Ref. 2019-1-TR01-KA202-076789) and to Mrs. Elena Krishnevskaya for her outstanding collaboration in rare anaemia research and unconditional support for the preparation of this manuscript.
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This is a revision that includes the mention of different papers published by the authors in the “Escola Professional d’Hematologia Farreras Valenti” (University of Barcelona, 1983) under the leadership of Prof. Ciril Rozman Borstnar. Accordingly, the inclusion of ethical approval is not required here.
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Corrons, J.V., Casafont, L.B. & Frasnedo, E.F. Concise review: how do red blood cells born, live, and die?. Ann Hematol 100, 2425–2433 (2021). https://doi.org/10.1007/s00277-021-04575-z
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DOI: https://doi.org/10.1007/s00277-021-04575-z
Keywords
- Erythrocytes
- Ageing
- Deformability
- Bone marrow
- Spleen electron microscopy