A role for complement as the major opsonin in the sequestration of erythrocytes from elderly and young donors

Abstract

Erythrocytes from elderly donors (> 70 years), but not young donors (18-35 years), are shown to undergo sequestration in an in vitro erythrophagocytosis assay. Comparable levels of sequestration are observed for high density erythrocytes from young individuals and both low density and high density erythrocytes from elderly individuals. These cells, which are susceptible to phagocytosis with no additional treatment are collectively termed 'in situ aged' erythrocytes. We present evidence for the involvement of complement in the sequestration of 'in situ aged' erythrocytes and correlate levels of complement bound to 'in situ aged' erythrocytes from young and elderly donors with levels of phagocytosis. We also demonstrate that the in vitro sequestration of erythrocytes from elderly donors can be inhibited by beta-galactosyl sugars and arginine-glycine-aspartic acid (RGD) but not by mannose nor by Protein-G, a specific inhibitor of Fc-gamma mediated phagocytosis. These experiments show that IgG is not the major opsonin in the sequestration of red cells from elderly donors. In support of the role of complement rather than IgG as the major opsonin in red cell sequestration, we further demonstrate that C'3 bearing immune complexes block in vitro sequestration of erythrocytes from elderly donors. This competition is not dependent upon the isotype of the immunoglobulin (IgM or IgG) in the complex but rather on the presence of active complement.