Mechanisms for the removal of senescent human erythrocytes from circulation: Specificity of the membrane-bound immunoglobulin G

Khansari, Nemat; Springer, Georg F.; Merler, Ezio; Fudenberg, H. Hugh

doi:10.1016/0047-6374(83)90015-5

Cited by 28 publications

(17 citation statements)

References 24 publications

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“…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)(3)(4)(5)(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).…”

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confidence: 99%

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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Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

et al. 1988

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“…In newborns, vitamin E deficiency causes a hemolytic anemia that develops by 4 to 6 weeks of age (46). Specific biochemical alterations in the membrane of erythrocytes from vitamin E-deficient rhesus monkeys have been described (47,48 16,20, and 30 wk after being placed on their assigned diet. Rats fed a diet containing no vitamin E are referred to as "deficient" rats, those…”

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confidence: 99%

“…The "neo-antigen" is recognized by the antigen binding, Fab, region (3,10,11) of a specific IgG autoantibody in serum that attaches to it and initiates the removal of cells by macrophages (1)(2)(3)(4). A number of studies performed by us (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and by others have demonstrated the presence of IgG on senescent, damaged, and stored erythrocytes (12)(13)(14)(15)(16)(17)(18)(19)(20)1). In addition, workers in several laboratories have recently presented evidence that IgG binding is also involved in the removal of erythrocytes in diseases such as thalassemia (21) and sickle cell anemia (22,23).…”

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confidence: 99%

Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.

Kay¹,

Bosman²,

Shapiro³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

101

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Senescent-cell antigen is a "neo-antigen" that appears on the surface of senescent cells and initiates IgG binding and cellular removal. As an approach to evaluating oxidation as a possible mechanism for generation of senescentcell antigen, we studied erythrocytes from vitamin E-deficient rats. Vitamin E is localized primarily in cellular membranes. Its major role is the termination of free-radical chain reactions propagated by the polyunsaturated fatty acids of membrane phospholipids. Results of our studies indicate that erythrocytes of all ages from vitamin E-deficient rats behave like old erythrocytes from normal rats, as determined by their susceptibility to phagocytosis, IgG binding, anion transport ability, and glyceraldehyde-3-phosphate dehydrogenase activity. Increased breakdown products of band 3 were observed with immunoblotting in membranes of erythrocytes from vitamin E-deficient rats. Breakdown products of band 3 are known to increase as cells age in normal individuals. The data suggest that oxidation may be a possible mechanism for erythrocyte aging and generation of senescent-cell antigen in vivo.

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“…In addition to aberrant glycoslation, there is another way, that may lead to the exposure of Tn and T EPs on cells. Previous studies have documented that sialic acid may be released from major sialoglycoproteins of erythrocyte membranes as the result of cell aging (Gattegno et al 1979;Khansari et al 1983). On desialylation of the RBC membrane, T Ag and some Tn Ag is unmasked (Springer and Desai 1982).…”

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confidence: 99%

Quantitative Computerized Image Analysis of Tn and T (Thomsen–Friedenreich) Epitopes in Prognostication of Human Breast Carcinoma

Wang

Springer

Carlstedt

1997

J Histochem Cytochem.

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SUMMARYThe precursors of the blood group N and M-immunodominant structures, Tn and T (Thomsen-Friedenreich) epitopes (EPs) occur in ‫ف‬ 90% of carcinomas (CAs) but are masked in benign-diseased and healthy tissues. We determined quantitatively on 55 primary invasive ductal breast CAs, stages I to IV, the prognostic value of extent of Tn and T EP expression over an observation period exceeding 5 years postoperatively. Classical, established pathological and histological prognostic characteristic indicators associated with survival were subdivided by standard criteria into favorable and unfavorable categories. Tissue sections were reacted with monoclonal anti-Tn and -T antibodies, followed by the streptavidin-biotin-peroxidase-DAB procedure; counterstain was methyl green. Tn and T EPs were then quantitated by computerized image analysis. Of the 55 CAs, 51 clearly expressed Tn and T, and four had traces. Strong Tn EP expression was statistically significantly associated with shortened 5-year disease-free interval, increasing pTNM stages, positive lymph node status, and increasing combined histological grades. T EPs were usually well expressed but showed no significant association with prognostic factors. Our results suggest that quantitative immunohistochemistry-image analysis of Tn EPs of primary breast CAs may add new parameters to prognostication. (J Histochem Cytochem 45:1393-1400, 1997)

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Mechanisms for the removal of senescent human erythrocytes from circulation: Specificity of the membrane-bound immunoglobulin G

Cited by 28 publications

References 24 publications

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

Cellular Dehydration and Immunoglobulin Binding in Senescent Neonatal Erythrocytes

Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.

Quantitative Computerized Image Analysis of Tn and T (Thomsen–Friedenreich) Epitopes in Prognostication of Human Breast Carcinoma

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