The kinetics for binding and catabolism of aggregated IgG by rat peritoneal macrophages
Knutson, D.W.; Kijlstra, A.; van Es, L.A.
Journal of Immunology 123(5): 2040-2048
1979
ISSN/ISBN: 0022-1767 PMID: 489969 Document Number: 139868
Mononuclear phagocytes in the 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 .mu.g) at 37.degree. C for 10 min to 24 h with 1.0 .times. 106 adhering peritoneal macrophages from normal rats. A-IgG were 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 rate-limiting step (binding rate constant = ka = 0.7 to 5.5 .times. 10-3/min; catabolism rate constant = kc = 20.0 to 55.0 .times. 10-3/min). 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 .mu.g but fewer molecules of A-IgG9 could be cleared per unit time than A-IgG74 (1200 A-IgG9 and 540 A-IgG74 molecules/cell per min). Most cell-associated A-IgG were present on the cell surface where they were accessible to release by trypsin. Binding may become 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, pinocytosis of A-IgG may be slower than the subsequent catabolic step. Bound A-IgG may be pinocytosed at a constant fractional rate. This may require mechanisms to concentrate A-IgG at certain sites on the membrane and selectively interiorize the A-IgG bearing portions.