Recognition Signals for Phagocytic Removal of Favic Malaria-Infected and Sickled Erythrocytes

According to a recently published concept (1), immunologicallymediated erythrocyte (RBC) removal involves binding of autologous, naturally circulating antibodies directed against normally hidden epitopes of integral RBC membrane proteins. Prerequisite of antibody binding are modifications of specific RBC proteins, presumably band 3 and the glycophorins. The exact nature of the modifications resulting in exposure of hidden epitopes or generation of neoantigenic sites, is still unknown. Evidence that oxidant-elicited oligomerization of band 3 is a sufficient change to enhance anti-band 3 binding has been provided (2,3). The precise molecular composition of the opsonin complex, and the nature of the bonds which keep its components together, are poorly defined as yet. An essential characteristic of the anti-band 3-mediated removal is the precipitation of complement (1–3). Indeed, conditions that inactivate complement convertases and abrogate the formation of the active complement component C3b also extensively inhibit phagocytic removal of variously damaged RBC. The same inhibition of phagocytosis occurs after blockage of the C3b receptor (CR1, complement receptor type one) on the macrophage surface (3,4). Lutz et al.(2,3–5) hypothesized that anti-band 3 antibodies bivalently bound to aggregated band 3 stimulate generation and deposition of activated C3 on the RBC surface.