Red Cell Spectrin Phosphorylation and Cytoskeletal Anchorage

101

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.

Section: Discussionmentioning

confidence: 74%

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

101

“…Antibodies to erythrocyte membrane constituents are present in normal human serum (1)(2)(3)(4)(5). Some of them opsonize senescent or damaged erythrocytes and induce engulfment of the cells by phagocytes (3)(4)(5).…”

mentioning

confidence: 99%

Naturally occurring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes.

Lutz

Bussolino

Flepp

et al. 1987

224

159

Treatment of erythrocytes with the thiolspecific oxidant azodicarboxylic acid bis(dimethylamide) (diamide) enhances their phagocytosis by adherent monocytes. Phagocytosis of diamide-treated erythrocytes required that the cells were opsonized with whole serum, since complement inactivation abolished phagocytosis. Opsonization with whole serum containing 20-100 times the physiological concentration of naturally occurring anti-band-3 antibodies enhanced phagocytosis of diamide-treated erythrocytes. High inputs of antiband-3 also restored phagocytosis oferythrocytes that had been incubated with complement-inactivated serum. Elevated concentrations of anti-spectrin antibodies were ineffective in whole and complement-inactivated serum.

“…Some NAAb are directed against easily accessible autoconstituents (e.g., soluble plasma proteins, hormones, surface components of senescent red blood cells, fetal cells, and tumor cells) (2). Other NAAb react with hidden self antigens (e.g., cytoskeletal and other nuclear antigens or cryptic membrane epitopes exposed after proteolytic enzyme treatment) (3).…”

mentioning

confidence: 99%

Two murine natural polyreactive autoantibodies are encoded by nonmutated germ-line genes.

Baccalà

Quang

Gilbert

et al. 1989

135