Senescent cell antigen is immunologically related to band 3.

Kay, Marguerite M. B.; Goodman, Steven R.; Sørensen, Keld E.; Whitfield, Carol F.; Wong, Patrick; Zaki, Laila; Rudloff, Victor

doi:10.1073/pnas.80.6.1631

Cited by 154 publications

(104 citation statements)

References 37 publications

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“…However, they do not agree on the molecular changes responsible for generating the antigen. Our evidence suggests that senescent-cell antigen is derived from band 3, probably by degradation (10,(25)(26)(27)(28)(29)(30)(31); Lutz and his colleagues have suggested that senescent-cell antigen is a dimer ofband 3 (32); Sayare et al (33) have shown that band 3 can cross-link with hemoglobin under oxidative conditions; and Low et al (34) have presented evidence that clustered band 3 can generate senescent-cell antigen. These membrane events are not mutually exclusive.…”

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confidence: 76%

“…Senescent-cell antigen is a glycosylated 4.5 region polypeptide that appears to be derived from band 3 (5,8,10,(25)(26)(27). Senescent-cell antigen is located on an extracellular portion of band 3 that includes most ofthe 38-kDa carboxyl-terminal segment and 30% ofthe anion-transport region (27).…”

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confidence: 99%

“…These membrane events are not mutually exclusive. Indeed, we have postulated that generation of senescent-cell antigen may result from oxidation-induced cross-linking followed by proteolysis (26).…”

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confidence: 99%

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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.

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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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confidence: 76%

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confidence: 99%

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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.

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101

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“…There is strong evidence that naturally occurring antibodies recognizing senescent RBCs in vivo recognize Band 3. 38 Thus, we used the antimouse Band 3 mAb 34-3C for opsonization, a mAb that induces RBC phagocytosis both in vivo and in vitro and shows enhanced binding to aged murine RBCs in vivo. 23,28,31 In the presence of serum, phagocytosis of IgG-opsonized WT Ox-RBCs was increased, compared with equally opsonized untreated WT RBCs (84.3 Ϯ 8.0 vs 52.3 Ϯ 0.5 RBCs/100 macrophages, respectively; P Ͻ .05) ( Figure 4A).…”

Section: Cd47 On Ox-rbcs Can Still Inhibit Fc␥r-mediated Phagocytosismentioning

confidence: 99%

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

Olsson

Oldenborg

2008

Blood

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IntroductionRemoval of senescent red blood cells (RBCs) from the circulation is a selective process mediated mainly by macrophages in the liver and spleen. 1 Several molecular patterns, which may be involved as ligands in recognition by macrophages, appear on the surface of senescent RBCs. Macrophages can either directly recognize these ligands, or recognition can be dependent on binding of bridging plasma proteins that may interact with the RBC ligands. [2][3][4][5][6][7] As such, these RBC ligands may include alterations in protein carbohydrate moieties, 8 loss of plasma membrane phospholipid asymmetry, [9][10][11] and/or clustering of Band 3 with subsequent binding of complement or antibodies. 12-14 Phagocytosis by macrophages can for instance be induced following ligation of receptors such as Fc␥ receptors (Fc␥R), complement receptors, or scavenger receptors (SRs). [15][16][17] Fc␥R recognizes the Fc portion of immunoglobulin G (IgG) bound to a target cell, resulting in rapid phagocytosis of the IgG-opsonized target. SRs make up a large family of receptors with a broad ligand-binding ability, where most known ligands are polyanionic molecules such as proteins, polyribonucleotides, polysaccharides, and lipids. 16 "Altered" host molecules (eg, oxidized low-density lipoprotein [oxLDL]) can be recognized by most SRs, whereas other ligands interact more specifically with SRs. 16 Oxidative damage is likely to be one important cause of RBC senescence and exposure of senescence-associated ligands. 13,18 RBCs oxidized in vitro (Ox-RBCs) are efficiently phagocytosed by macrophages in the absence of further opsonization, a process shown to be inhibited by oxLDL or other SR ligands, such as fucoidan, dextran sulfate, or poly-I, both in vivo and in vitro. 4,7,19 Phagocytosis of Ox-RBCs has also been suggested to be serum dependent, 6 and involve recognition of phosphatidylserine (PS) on the RBC surface. 9,10 Macrophage phagocytosis of target host cells is regulated by the balance between signaling through prophagocytic receptors (eg, Fc␥R or complement receptors) and inhibitory receptors. Recognition of the cell surface glycoprotein CD47 by the inhibitory receptor signal regulatory protein alpha (SIRP␣) inhibits phagocytosis of unopsonized RBCs, as well as IgG or complementopsonized RBCs, both in vivo and in vitro. 20-23 CD47 is highly expressed on RBCs, but ubiquitously expressed by most cells in the body, and can also negatively regulate phagocytosis of platelets and leukocytes. [24][25][26] The amount of CD47 on the cell surface regulates macrophage phagocytosis, since IgG-opsonized RBCs from CD47 ϩ/Ϫ mice (expressing about 50% of normal levels of CD47) are taken up faster than wild-type (WT) RBCs, but slower than CD47 Ϫ/Ϫ RBCs. 27 We have shown that the phagocytosis-inhibitory effect of CD47 does not come into play on apoptotic nucleated cells, where CD47 is clustered into patches on the apoptotic cell surface and segregated away from prophagocytic ligands such as PS or calreticulin. 25 Although older circulating RBC...

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“…The antigen in fact is recognized by the Fab region of autologous specific IgG [5,6] which attaches to it and initiates the removal of cells by macrophages. Senescent cell antigen is immunologically related to band 3 [3,7] and is located in an extracellular portion of it [3]. The molecular changes underlying the formation of senescent cell antigen and marking erythrocytes as aged are under investigation.…”

Section: Introductionmentioning

confidence: 99%

Iron release, membrane protein oxidation and erythrocyte ageing

et al. 1995

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The aerobic incubation of erythroeytes in phosphate buffer for 24-60 h (a model of rapid in vitro ageing) induced progressive iron release and methemoglobin formation. Membrane proteins showed electrophoretic alterations and increase in carbonyl groups (as documented by IR spectroscopy). None of these phenomena were seen when the erythrocytes were incubated under anaerobic conditions. The membranes from aerobically incubated cells bound a much higher amount of autologous IgG than those from anaerobically incubated ones, suggesting that the aerobic incubation gives rise to the senescent antigen. The addition of ferrozine during the aerobic incubation prevented both the IgG binding and the protein alterations seen in the IR spectra, suggesting an intracellular chelation of the released iron by ferrozine.

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Senescent cell antigen is immunologically related to band 3.

Cited by 154 publications

References 37 publications

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

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

CD47 on experimentally senescent murine RBCs inhibits phagocytosis following Fcγ receptor–mediated but not scavenger receptor–mediated recognition by macrophages

Iron release, membrane protein oxidation and erythrocyte ageing

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