How are immune complexes bound to the primate erythrocyte complement receptor transferred to acceptor phagocytic cells?

Immune complexes (IC) bound to the primate erythrocyte (E) complement recep tor (CR1) are cleared from the circulation of primates and localized to pha gocytic cells in the liver and spleen without E destruction. IC can be boun d to E CR1 either via C3b opsonization or with cross-linked mAb complexes ( heteropolymers, HP) which contain a mAb specific for CR1 and a mAb specific for an antigen. The long-term goal of our work is to apply the HP system t o the treatment of human diseases associated with blood-borne pathogens. Th is review discusses the mechanism by which the E-bound IC are transferred t o acceptor cells. Our studies in animal models as well as our in vitro inve stigations indicate that IC transfer is rapid (usually >90% in 10 min) and does not lead to lysis or phagocytosis of the E. Experiments with specific inhibitors and the use of IC prepared with Fab' fragments suggest that tran sfer depends mainly upon recognition by Fc receptors on the acceptor cell. Moreover, we find that IC release from the E is associated with a concerted loss of CR1, and is followed by uptake and internalization of the IC by th e acceptor cell. We suggest that recognition and binding of the E-bound IC substrates by Fc receptors allows close contact between the E and acceptor cells, which in turn facilitates proteolysis of E CR1, presumably by a macr ophage-associated protease. After proteolysis, the released IC are internal ized by the macrophages. (C) 1999 Elsevier Science Ltd. All rights reserved .