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 receptor (CR1) are cleared from the circulation of primates and localized to phagocytic cells in the liver and spleen without E destruction. IC can be bound to E CRI either via C3b opsonization or with cross-linked mAb complexes (heteropolymers, HP) which contain a mAb specific for CRI and a mAb specific for an antigen. The long-term goal of our work is to apply the HP system to the treatment of human diseases associated with blood-borne pathogens. This review discusses the mechanism by which the E-bound IC are transferred to acceptor cells. Our studies in animal models as well as our in vitro investigations 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 transfer 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 the 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 macrophage-associated protease. After proteolysis, the released IC are internalized by the macrophages.
Nardin
A
A
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville 22908, USA.
Lindorfer
M A
MA
Taylor
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000378:metabolism; D001693:Biological Transport, Active; D001792:Blood Platelets / Q000276:immunology; D003179:Complement C3b / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D010586:Phagocytes / Q000276:immunology*; D011323:Primates; D017463:Receptors, Complement 3b / Q000097:blood* / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D003179:Complement C3b