Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio.

Mueller, Thomas; Jackson, Carl W.; Dockter, Michael E.; Morrison, Martin

doi:10.1172/jci112839

Cited by 88 publications

(50 citation statements)

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“…Thus, demonstrating a correlation between erythrocyte enzyme levels and density may confirm an enrichment of young cells at the top of a density gradient, but may not define the relative age of denser cells. Recently, studies of red cells from mouse and from man have suggested that the ratio of protein 4.la to 4.lb is an internal aplasia have exceptionally high ratios of 4.la to 4.lb indicate marker of cell age; as erythrocytes circulate, progressively more that this ratio reflects the aging process of mature red cells as protein 4. l a is present in the cells (23,24). The findings of well as the process of reticulocyte maturation.…”

Section: Discussionmentioning

confidence: 85%

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

et al. 1988

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ABSTRACT. The life span of neonatal erythrocytes (60-80 days) is shorter than that of adult erythrocytes (120 days). We studied neonatal red blood cells separated on stractan density gradients to further characterize the aging process and to explore the possibility that senescence antigens play a role in the destruction of neonatal erythrocytes. Quantitation of membrane proteins 4.la and 4.lb served as a marker for cell age and confirmed an enrichment for senescent red cells in the most dense layers of the gradients. Despite the shorter life span of neonatal erythrocytes, cord blood contained a larger percentage of very dense, K+-depleted red cells than did adult blood. ATP levels in dense neonatal and adult cells were decreased to 50-80% of normal values for unseparated red cells. Levels of reduced glutathione did not fall with increasing cell density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of red cell membrane proteins showed increased membrane-associated globin in senescent neonatal cells, but such gels run without reducing agents did not show oxidative protein cross-linking. Membrane bound immunoglobulins were detected on senescent neonatal and adult red cells by the rosetting antiglobulin test. We conclude that senescence antigens are revealed during the aging process of neonatal erythrocytes, thereby labeling them for antibody-mediated destruction in the reticuloendothelial system. (Pediatr Res 23: 288-292, 1988) Abbreviations GSH, reduced glutathione SDS, sodium dodecyl sulfate PAGE, polyacrylamide gel electrophoresis BSKG, buffered saline with potassium and glucose EA, erythroctye antibody DTT, dithiothreitol RBC, red blood cells Normal human red cells undergo a nonrandom, age-dependent process of removal from the circulation; the most aged or senescent cells are selectively destroyed (1). The sequence of events that targets the senescent erythrocyte for destruction is not completely understood, but recent work has suggested that aging of adult red cells is associated with the exposure of cryptic, senescence antigens on the exterior surface of the red cell membrane (2-6). Such antigens are then recognized by autologous immunoglobulins, thus facilitating the removal of aged cells by the macrophages of the reticuloendothelial system (2-6).The life span of neonatal red cells is significantly shorter than that of adult red cells. While adult erythrocytes survive in the circulation for 120 days, fetal cells survive only 60-80 days (7-9). The mechanisms underlying the shorter survival are unknown, but cross-transfusion experiments have indicated that the decreased life span is intrinsic to the fetal cell, rather than a feature of the fetal circulation (8).Recently, Matovcik et al. (10) studied density-separated red cells and showed that the aging process of human neonatal erythrocytes is associated with a more rapid loss of membrane surface area than is the case with adult red cells. The loss of surface area was demonstrated to have a significant detrimental effect on cell deformability. ...

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Section: Discussionmentioning

confidence: 85%

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

et al. 1988

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“…33,34 In the original protocol 33,34 about 50 mice were used for serial transfusions to yield one animal enriched for sRBC. In our optimized protocol, we used only 10 mice for the same purpose.…”

Section: Discussionmentioning

confidence: 99%

“…32 In addition, the arrest of erythropoiesis by hypertransfusion was used to enrich blood with naturally aged RBC that could be characterized. 33,34 RBC from such treated rats and mice showed alterations in membrane components such as changes in the band 4.1a to 4.1b ratio and decreased cell volume, but they were not used to elucidate the mechanism of EPC.…”

Section: Introductionmentioning

confidence: 99%

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Gottlieb¹,

Topaz²,

Cohen³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe lifespan of red blood cells is terminated when macrophages remove senescent red blood cells by erythrophagocytosis. This puts macrophages at the center of systemic iron recycling in addition to their functions in tissue remodeling and innate immunity. Thus far, erythrophagocytosis has been studied by evaluating phagocytosis of erythrocytes that were damaged to mimic senescence. These studies have demonstrated that acquisition of some specific individual senescence markers can trigger erythrophagocytosis by macrophages, but we hypothesized that the mechanism of erythrophagocytosis of such damaged erythrocytes might differ from erythrophagocytosis of physiologically aged erythrocytes. Design and MethodsTo test this hypothesis we generated an erythrocyte population highly enriched in senescent erythrocytes by a hypertransfusion procedure in mice. Various erythrocyte-aging signals were analyzed and erythrophagocytosis was evaluated in vivo and in vitro. ResultsThe large cohort of senescent erythrocytes from hypertransfused mice carried numerous aging signals identical to those of senescent erythrocytes from control mice. Phagocytosis of fluorescently-labeled erythrocytes from hypertransfused mice injected into untreated mice was much higher than phagocytosis of labeled erythrocytes from control mice. However, neither erythrocytes from hypertransfused mice, nor those from control mice were phagocytosed in vitro by primary macrophage cultures, even though these cultures were able to phagocytose oxidatively damaged erythrocytes. ConclusionsThe large senescent erythrocyte population found in hypertransfused mice mimics physiologically aged erythrocytes. For effective erythrophagocytosis of these senescent erythrocytes, macrophages depend on some features of the intact phagocytosing tissue for support. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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“…Since the discovery that the ratio of protein 4.1a to protein 4.1b, which are a part of the red cell membrane cytoskeleton, is correlated with erythrocyte life span in mammals [7][8][9], several authors have adopted the 4.1a/4.1b ratio as a parameter to characterize the absolute age of density-fractionated human erythrocytes [10][11][12]. Results obtained so far have shown that the population of circulating red cells is in fact very heterogeneous, with respect to membrane surface, cell volume, cation and water content, and cell deformability [12,13].…”

Section: Introductionmentioning

confidence: 99%

Cellular properties of human erythrocytes preserved in saline–adenine–glucose–mannitol in the presence of L‐carnitine

Arduini¹,

Minetti

Ciana

et al. 2006

American J Hematol

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L-Carnitine (LC) in the preservation medium during storage of red blood cells (RBC) can improve the mean 24-hr percent recovery in vivo and increase RBC life-span after reinfusion. The purpose of the study was to investigate the differences in the biochemical properties of RBCs stored in the presence or absence of LC, and the cell-age related responses to storage conditions and to LC. RBC concentrates in saline-adenine-glucose-mannitol (SAG-M) were stored in the presence or absence of 5 mM LC at 48C for up to 8 weeks. RBC subpopulations of different densities were prepared by centrifugation on Stractan density gradient. Cells were sampled at 0, 3, 6, and 8 weeks, and hematological and cellular properties analyzed (MCV, MCHC, 4.1a/4.1b ratio as a cell age parameter, intracellular Na + and K + ). After 6 weeks, MCV of RBC stored in the presence of LC was lower than that of controls (6 weeks MCV: controls 95.4 ± 1.8 fl; LC 91.5 ± 2.0 fl; n = 6; P < 0.005). This was due to swelling of control cells, and affected mainly older RBCs. LC appeared to reduce or retard cell swelling. Among the osmotically active substances whose changes during storage could contribute to cell swelling, only intracellular Na

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Membrane skeletal alterations during in vivo mouse red cell aging. Increase in the band 4.1a:4.1b ratio.

Cited by 88 publications

References 26 publications

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Cellular properties of human erythrocytes preserved in saline–adenine–glucose–mannitol in the presence of L‐carnitine

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