Antibody Dependent Cell Mediated Cytotoxicity and Phagocytosis of Senescent Erythrocytes by Autologous Peripheral Blood Mononuclear Cells

Abstract

Human red blood cells (RBCs) have a life span of 120 days in circulation, after which they are removed primarily by resident macrophages. Autoimmune antibodies are commonly found on effete RBCs and appear to contribute to their removal from the circulation. In this article, we focused on senescent erythrocytes and studied their removal, in comparison to young RBCs, in two RBC-depletion in vitro assays: antibody dependent cell mediated cytotoxicity (ADCC) and erythrophagocytosis. The results were determined prior to and following the addition of anti-D antibodies to the systems. Old (O-RBC) and young (Y-RBC) erythrocytes were separated by differential centrifugation. When incubated with autologous peripheral blood mononuclear cells as attacking cells, both anti-D treated O-RBCs and anti-D treated Y-RBCs were phagocytized and underwent contact lysis. However, O-RBCs had a significantly higher tendency to be phagocytized ( p =0.05) and a higher predisposition to undergo lysis ( p =0.043) than did Y-RBCs. When incubated with attacking cells without anti-D antibodies, O-RBCs were phagocytized while Y-RBCs were not phagocytized at all ( p =0.046). No contact lysis of either source of target cells occurred when incubated with attacking cells alone without anti-D sera. These in vitro results suggest that ADCC may serve as an additional pathway of elimination of senescent erythrocyte in addition to the classical phagocytosis pathway.

• Adcc
• Erythrophagocytosis
• Senescent Erythrocytes
• Young Erythrocytes