Erythrocyte Aging: A More than Superficial Resemblance to Apoptosis?

Bosman, G.J.C.G.M.; Willekens, F. L. A.; Werre, J. M.

doi:10.1159/000087725

Cited by 212 publications

(159 citation statements)

References 38 publications

(39 reference statements)

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“…An examination of erythrocyte size by FACS showed that the heterogeneity of erythrocyte sizes increased during aging in SOD1 −/− mice and that the average sizes were larger than those in SOD1 +/+ mice (Figure 1B). Since enlargement is a characteristic of aged erythrocytes that are efficiently trapped by the reticuloendothelial system followed by destructive elimination [28], these data suggest that the accelerated destruction of erythrocytes is the cause of the anaemia. In contrast with erythrocytes, the blood levels of reticulocytes ( Figure 1C) as well as platelets (results not shown) were significantly high and were increased with aging.…”

Section: Anaemic Phenotype Of Sod1-deficient Micementioning

confidence: 92%

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Iuchi

Okada

Onuma

et al. 2007

Biochemical Journal

150

105

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Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, SOD1 −/− mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1 −/− mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD1 deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase II, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.

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Section: Anaemic Phenotype Of Sod1-deficient Micementioning

confidence: 92%

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Iuchi

Okada

Onuma

et al. 2007

Biochemical Journal

150

105

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“…The life span of erythrocytes amounts to some 100-120 days, that is, each day more than 200 billion erythrocytes need to be replaced, containing almost 20 mL of packed cell volume. Erythrocytes are considered to undergo senescence eventually resulting in the clearance of aged erythrocytes (1)(2)(3). Beyond that, erythrocytes are, similar to nucleated cells, cleared by suicidal death.…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte programmed cell death

2008

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“…These include oxidation of band 3, leading to naturally occurring antibody-mediated opsonization followed by Fc-receptor mediated phagocytosis, and programmed or suicidal cell death. [1][2][3] Because RBC lack a nucleus and mitochondria, they do not undergo 'classic' apoptosis. However, features of programmed cell death have also been proposed for RBC ('eryptosis').…”

Section: Introductionmentioning

confidence: 99%

A role for activated endothelial cells in red blood cell clearance: implications for vasopathology

Fens¹,

Wijk²,

Andringa³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundPhosphatidylserine exposure by red blood cells is acknowledged as a signal that initiates phagocytic removal of the cells from the circulation. Several disorders and conditions are known to induce phosphatidylserine exposure. Removal of phosphatidylserine-exposing red blood cells generally occurs by macrophages in the spleen and liver. Previously, however, we have shown that endothelial cells are also capable of erythrophagocytosis. Key players in the erythrophagocytosis by endothelial cells appeared to be lactadherin and αv-integrin. Phagocytosis via the phosphatidylserine-lactadherin-αv-integrin pathway is the acknowledged route for removal of apoptotic innate cells by phagocytes. Design and MethodsEndothelial cell phagocytosis of red blood cells was further explored using a more (patho)physiological approach. Red blood cells were exposed to oxidative stress, induced by tert-butyl hydroperoxide. After opsonization with lactadherin, red blood cells were incubated with endothelial cells to study erythrophagocytosis and examine cytotoxicity. ResultsRed blood cells exposed to oxidative stress show alterations such as phosphatidylserine exposure and loss of deformability. When incubated with endothelial cells, marked erythrophagocytosis occurred in the presence of lactadherin under both static and flow conditions. As a consequence, intracellular organization was disturbed and endothelial cells were seen to change shape ('rounding up'). Increased expression of apoptotic markers indicated that marked erythrophagocytosis has cytotoxic effects. ConclusionsActivated endothelial cells show significant phagocytosis of phosphatidylserine-exposing and rigid red blood cells under both static and flow conditions. This results in a certain degree of cytotoxicity. We postulate that activated endothelial cells play a role in red blood cell clearance in vivo. Significant erythrophagocytosis can induce endothelial cell loss, which may contribute to vasopathological effects as seen, for instance, in sickle cell disease.

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Erythrocyte Aging: A More than Superficial Resemblance to Apoptosis?

Cited by 212 publications

References 38 publications

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Erythrocyte programmed cell death

A role for activated endothelial cells in red blood cell clearance: implications for vasopathology

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