Phagocytosis of 'old' red blood cells by macrophages from syngeneic mice in vitro.

We have studied in vitro the interaction of peritoneal macrophages with 'old' and 'young' RBC, as well as with enzymatically treated 'old' and 'young' RBC from syngeneic mice. 'Old' RBC were recognized and phagocytized by macrophages, whereas 'young' RBC were not. Neuraminidase treatment of both 'young' and 'old' RBC had little effect on the extent of phagocytosis. Trypsin treatment, on the other hand, markedly reduced the phagocytosis of 'old' RBC and had no effect on the phagocytosis of 'young' RBC. The level of phagocytosis of 'old' RBC by macrophages from mineral-oil treated mouse peritoneal cavities was roughly half that of macrophages from untreated mice. It is postualted that 'old' RBC could be recognized due to the presence of cytophilic antibodies on the surface of the macrophages. The specificity of these hypothetical cytophilic antibodies is believed to be directed towards sites which are absent or shielded in 'young' RBC, and exposed in 'old' RBC. Trypsin treatment of 'old' RBC appears to remove these antigenic sites from the 'old' RBC. The lower level of phagocytosis of 'old' RBC by mineral-oil induced macrophages could be due to the previous phagocytic activity of these cells, and their relatively uncoated, newly form plasma membrane, lacking cytophilic antibodies. In support of this hypothesis, we have demonstrated that trypsin treatment of macrophages resulted in a markedly decreased phagocytosis of 'old' RBC.