Macrophage-alloantibody-target cell interactions. III. Stripping of antibody-coated cells by human macrophages

Abstract

In earlier studies on rodents it was established that macrophages could have either destructive or protective effects on antibody-coated nucleated cells. The present studies were initiated to determine which of these effects predominated with human macrophages. Macrophage-rich peritoneal cell suspensions from peritoneal dialysis fluid were incubated with alloantibody-coated human lymphocyte target cells. The lymphocytes were not lysed, although as expected the peritoneal cells could lyse or phagocytize antibody-coated human erythrocytes. Nevertheless, the peritoneal cells did interact vigorously with the lymphocyte target cells, since the latter rapidly became resistant to lysis by complement. Such resistance was not due to engulfment of whole target cells by macrophages, since the target cells could still be lysed by complement when a second antibody was added. The development of resistance to complement lysis was a temperature- and time-dependent, Fc receptor mediated effect of adherent cells, and was inhibitable by cytochalasin B and various metabolic inhibitors. These results indicate that the principal action of human macrophages on antibody-coated nucleated human cells is inactivation or removal of the antibody bound to the target cell membrane, resulting in protection of the target cells from antibody-dependent destruction. However, it is possible that the observed protection was produced only at the expense of subtle, non-lethal membrane damage, since small but significant increases in osmotic fragility of the target cells were frequently demonstrable after incubation with macrophages.