Recognition and sequestration of young and old erythrocytes from young and elderly human donors: in vitro studies

Experiments were performed to determine the mechanism of recognition for sequestration of erythrocytes from elderly and young donors and to study in vitro a previously observed shortening of in vivo life span of erythrocytes in elderly donors. Erythrocytes from young and elderly human donors were separated according to their age-density on Stractan gradients. Elderly donors had more low age-density erythrocytes than did young donors. Erythrocytes from elderly donors had higher levels of immunoglobulin G (IgG) on their erythrocytes than did those from young donors. In an in vitro erythrophagocytosis assay, young (low age-density) and old (high age-density) erythrocytes from elderly donors and old but not young erythrocytes from young donors were recognized and sequestered. Phagocytosis of erythrocytes from elderly and young donors can be specifically blocked by beta-galactoside but not alpha-galactoside sugars. This phagocytosis is not blocked by protein G, which specifically blocks Fc-gamma-mediated erythrophagocytosis, thus demonstrating that the recognition of the senescent erythrocyte is not due to the direct recognition of a physiologic autoantibody. beta-Galactoside and alpha-galactoside sugars have no inhibitory effect on erythrophagocytosis mediated by IgG anti-Rh-D antibodies. Erythrophagocytosis of young and old erythrocytes from elderly donors and old erythrocytes from young donors are all mediated by a macrophage receptor with lectin-like properties, which can be inhibited by a beta-galactoside-like sugar moiety, and not by an Fc receptor that recognizes erythrocyte-bound IgG.(ABSTRACT TRUNCATED AT 250 WORDS)