Erythrocyte Homeostasis: Antibody-Mediated Recognition of the Senescent State by Macrophages

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 15; pp. 5498 - 5501
• Main Authors: Singer, J. A., Jennings, L. K., Jackson, C. W., Dockter, M. E., Morrison, M., Walker, W. S.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1986; National Acad Sciences
• Subjects: Age; Ageing, cell death; Animals; Antibodies; Biological and medical sciences; Cell physiology; Chemical suspensions; Erythrocyte Aging; Erythrocytes; Erythrocytes - immunology; Fundamental and applied biological sciences. Psychology; Homeostasis; Immunoglobulin A - immunology; Immunoglobulin G - immunology; Immunoglobulins; Ingestion; Isotypes; Macrophages; Macrophages - physiology; Mice; Molecular and cellular biology; Peritoneal Cavity - cytology; Phagocytosis; Receptors, Cell Surface - physiology; Trypsin - metabolism; Cell recognition; Vertebrata; Mammalia; Mouse; Ageing; Rodentia; Red blood cell; Homeostasis; Mechanism; Phagocytosis; Macrophage
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.15.5498

We tested the hypothesis that the accumulation of bound autologous antibody on a ``senescent epitope'' identifies aged erythrocytes for phagocytic removal by macrophages. Erythrocytes were collected from mice maintained on a hypertransfusion protocol designed to yield cells of defined age. The mouse erythrocytes were assayed for the presence of bound antibody by measuring their susceptibility to ingestion by macrophages from mouse peritoneal exudates and by flow cytofluorometry. Both assays disclosed that only the oldest mouse erythrocytes bore detectable levels of antibody. Flow cytofluorometric analysis revealed that the frequency distribution of IgG isotypes bound to the cells reflected their levels in normal serum. Finally, treatment with trypsin abolished the ability of the macrophages to ingest erythrocytes aged in vivo. These findings support the hypothesis that antibody mediates the clearance of senescent mouse erythrocytes from the circulation and demonstrate that the presence of a trypsin-sensitive recognition structure on macrophages is an essential requirement in this homeostatic process.