[Elimination of old erythrocytes from the circulation: exposure of a cell-age specific antigen on aging erythrocytes].
Selective phagocytosis of senescent human red blood cells (RBC) requires a molecular alteration on the surface of aging RBC. This cell-age determining signal represents neither a surface-charge density change nor extensive desialylation, as assumed earlier. Since IgG autoantibodies have been detected which specifically bind to senescent RBC, the required surface alteration represents the exposure of a cell-age-specific antigen (CAS antigen). The CAS antigen has been identified as a membrane protein with apparent molecular weights of approximately 100 K or approximately 200 K. Immunoprecipitation of Triton extracts from chymotrypsin-treated RBC as well as preliminary peptide analyses of the surface 125I-iodinated part of a CAS-antigen enriched fraction suggest that the CAS antigen has the protein structure of protein band 3. The CAS-antigenic sites are not formed during senescence but are already present in young RBC. Exposure of the CAS antigen in senescent RBC appears to be due to an increased probability of CAS-antigen dimers. This apparently minor change is sufficient for the following reasons: IgG autoantibody binding to monomeric CAS antigen appears to be monovalent and transient. Thus, CAS antigens may even be exposed rather than cryptic on the surface of young RBC. In contrast, IgG autoantibodies form thermodynamically considerably more stable complexes with dimeric CAS antigen because of a bivalent binding. The dimerization probability of CAS antigens in the plane of the membrane can be increased experimentally by destroying the anchorage between integral membrane proteins and the cytoskeleton. This loss of anchorage is followed by drastically enhanced IgG-autoantibody binding.
D001324:Autoantigens / Q000276:immunology; D000939:Epitopes; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D008565:Membrane Proteins / Q000032:analysis; D013154:Spleen / Q000502:physiology
D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D008565:Membrane Proteins
Elimination alter Erythrozyten aus der Zirkulation: Freilegung eines zellater-spezifischen Antigens auf alternden Erythrozyten.