Studies in the rat of antibody-sensitized and N-ethylmaleimide-treated erythrocyte clearance by the liver: effects of immune complex infusion and complement activation

Abstract

The function of the hepatic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide (NEM)-treated erythrocytes and erythrocytes sensitized with a rat IgG2a monoclonal antibody (R2/15S) directed against the rat RT1Aa class I antigen. The clearance of the antibody-sensitized erythrocytes was biphasic, with the initial phase being rapid and complement dependent. This clearance was entirely hepatic and could be reduced or prevented by the infusion of cobra venom factor (CVF), complement fragments or small amounts of immune complexes, prepared either at equivalence or 10-fold antigen excess. NEM-treated cells were removed rapidly from the circulation of normal rats (t 1/2 6.2 +/- 0.4 min) and their clearance rate was not influenced by complement depletion. Most of the cells accumulated in the liver, although a small proportion (17%) was removed by the spleen. Immune complexes formed at equivalence or heat-aggregated human gamma globulin (HAGG) delayed the removal of these cells from the circulation, although significantly larger amounts of HAGG were required to do this. Antigen-excess immune complexes had no effect.