Erythrocyte Age-Dependent Changes of Membrane Protein 4.1: Studies in Transient Erythroblastopenia

Ravindranath, Yaddanapudi; Brohn, Frederick; Johnson, Robert M.

doi:10.1203/00006450-198703000-00014

Cited by 17 publications

(7 citation statements)

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“…The findings of well as the process of reticulocyte maturation. We have demonRavindranath et al (24) that children with transient red cell strated that stractan density gradient centrifugation yields sub-populations of erythrocytes with relative quantities of protein 4.la which increase with increasing cell density; cells from the most dense layers of the gradient (density > 1.1 10 g/ml) have the greatest amount of 4. la. These data indicate that such density separations provide subpopulations of red cells enriched for senescent erythrocytes.…”

Section: Discussionmentioning

confidence: 71%

“…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: 86%

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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: 71%

Section: Discussionmentioning

confidence: 86%

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

et al. 1988

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“…Conversely, the percent HbA1c has been used to estimate the relative age of isolated RBC subfractions [14]. The ratio of erythrocyte membrane Band 4.1a:4.1b is increased in the aged RBC present in the hypertransfused mouse model [17] and in transient erythroblastopenia of childhood [18], and is decreased in hemolytic anemias [19]. This has lead to the use of this ratio as an age marker in human RBC [20].…”

Section: Age-dependent Changes In Red Blood Cell Propertiesmentioning

confidence: 99%

The measurement and importance of red cell survival

2008

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The measurement of red blood cell survival in the circulation has progressed from the original differential agglutination technique of Ashby to current isotopic and flow cytometric methods. While occasionally useful in the clinic, these methods find widespread use in a number of important research areas, including the evaluation of new red cell storage media in transfusion medicine and studies of the pathophysiology of sickle cell disease and diabetes. In this review, measurement techniques are placed in historical perspective and examined for relative merits and suitable application. Am. J. Hematol. 84:109-114, 2009. V

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“…This has been demonstrated by increased band 4 . l a protein in RBC membrane of children with TEC (Ravindranath et al, 1987). In the present study, deformability (rheoscope) and density of RBCs were studied in seven children with TEC.…”

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confidence: 91%

Age dependency of red blood cell deformability and density: studies in transient erythroblastopenia of childhood

et al. 1993

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Several investigators have demonstrated that red blood cell (RBC) deformability decreases progressively with increasing cell density and proposed that reduction in deformability plays a role in the senescence process of normal RBCs. Transient erythroblastopenia of childhood (TEC) results from temporary cessation of erythropoiesis. Since no new RBCs are produced for some time, the circulating RBCs are relatively old. RBS density (phthalate-oil method) and RBC deformability (RBC elongation in a counter-rotating rheoscope) were studied in seven children with TEC and in 10 control children. The mean values of MCHC, RBC density and RBC deformation were not significantly different between TEC and control children. Compared to controls, the frequency distribution of RBC density in TEC was slightly shifted to higher values. The percentage of RBCs with extremely low densities (< 1.090 g/ml) was 0.9 +/- 1.2% in the patients and 5.6 +/- 2.3% in the controls (P < 0.001). The percentage of RBCs with high density (> 1.106 g/ml) was 6.4 +/- 2.1% in the patients and 4.9 +/- 1.8% in the controls (P > 0.10). The reduction of RBCs with low density in TEC suggests that RBCs with low density are relatively young. Since the percentage of RBCs with high density increased only slightly in TEC, we conclude that only a fraction of dense RBCs is old. In TEC, the frequency distribution of RBC elongation was slightly shifted to lower values. 5% of the RBCs studied in the control children had RBC elongation values above 0.39 (TEC 1.2%) and 5% had elongation values below 0.16 (TEC 6.7%). Thus, only a small fraction of highly deformable RBCs was diminished in TEC. These data suggest that a decrease in deformability is not a significant part of the normal ageing process of human RBCs.

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Erythrocyte Age-Dependent Changes of Membrane Protein 4.1: Studies in Transient Erythroblastopenia

Abstract: ABSTRACT. In high resolution sodium dodecyl sulfategel electrophoresis, the red cell protein, band 4

Cited by 17 publications

References 11 publications

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

The measurement and importance of red cell survival

Age dependency of red blood cell deformability and density: studies in transient erythroblastopenia of childhood

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