Mononuclear phagocytes in the reticuloendothelial system (RES) bind and catabolize circulating antigen-antibody complexes. These functions were studied with an in vitro model to elucidate the cellular mechanisms and rate-limiting step for catabolism of soluble immune complexes by mononuclear phagocytes. The model consisted of reacting stable heat aggregates of 125I-IgG (A-IgG) (0.01 to 10 µg) at 37°C for 10 min to 24 hr with 1.0 × 106 adhering peritoneal macrophages from normal rats. A-IgG were then separated into cell-associated, acid-precipitable (unreacted) and acid-soluble catabolized fractions. With subsaturating doses of A-IgG, binding and catabolism of A-IgG followed the kinetics for consecutive first-order reactions with binding the ratelimiting step (binding rate constant = ka = 0.7 to 5.5 × 10-3 min-1; catabolism rate constant = kc = 20.0 to 55.0 × 10-3 min-1). At higher doses of A-IgG, the binding step became saturated (and ka fell) while catabolism remained first order (with constant kc). The maximum clearance velocity (Vmax) was a function of A-IgG size in that more micrograms but fewer molecules of A-IgG9 could be cleared per unit time than A-IgG74 (1200 A-IgG9 and 540 A-IgG74 molecules per cell per min). Most cell-associated A-IgG were present on the cell surface where they were accessible to release by trypsin. On the basis of these observations, it was postulated that binding becomes saturated because of limited availability of receptors for the Fc portion of IgG. Assuming that pinocytosis of A-IgG was necessary before A-IgG were catabolized, these data further suggest that pinocytosis of A-IgG is slower than the subsequent catabolic step and that bound A-IgG are pinocytosed at a constant fractional rate. This would seem to require mechanisms to concentrate A-IgG at certain sites on the membrane and then selectively to interiorize the A-IgG bearing portions.

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This work was supported in part by a grant from the Dutch Kidney Foundation, Grant Number C72, and by a grant from the Kidney Foundation of Southern California.

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