Transfer of model immune complexes from erythrocyte complement receptor 1 to murine macrophages

Complement receptor 1 (CR1) on the surface of primate erythrocytes (E) binds antigen-antibody complexes (immune complexes, IC) that have been opsonized with complement fragment C3b. These E-bound IC are transported through the circulation to the liver where tissue macrophages remove the IC from the E and internalize the complexes. The E act as a means of transport for the IC and return to the circulation following the removal of the CR1-bound IC. Because the efficiency of IC binding by E is highly variable, our laboratory has developed a bispecific antibody complex (heteropolymer, HP) that functions to attach IC specifically to E CR1 with high affinity, and thereby, the HP facilitates clearance of IC from the circulation. To understand how the IC are removed from E CR1 by macrophages, an in vitro model of the transfer reaction has been established using P388D1 murine macrophages as the acceptor cell and bacteriophage &phis;X174 as the antigen. Through the use of this experimental system, the loss of &phis;X174, HP, and CR1 from the E has been demonstrated as well as the uptake of each of these components by the macrophages. The interaction of the Fc portion of IgG (contained within the HP) with the Fcgamma receptors (FcgammaR) on the macrophages is critical for the transfer process. Inhibition of the polymerization of actin filaments within the macrophages partially blocks IC transfer. Although opsonization of the IC with human complement normally facilitates in vivo clearance of IC, incubation of the E-IC with mouse complement in vitro leads to an inhibition of IC transfer to the mouse macrophages under otherwise identical conditions. Finally, transfer has been demonstrated both in solution phase as well as to adherent macrophages. Knowledge of the transfer reaction will facilitate the efficient clearance of a variety of pathogens from the circulation of humans.