Macrophage triggering by aggregated immunoglobulins. I. Delayed effect of IgG aggregates or immune complexes

Rat peritoneal macrophages in serum-free cultures were triggered to release lysosomal enzymes or plasminogen activator and to incorporate glucosamine upon exposure to rat IgG that was nonspecifically aggregated after heating or by dimethylsuberimidate cross-linking or was specifically complexed by the corresponding antigen using preformed BSA-anti-BSA immune complexes. A lag period of 6 hr was observed before the increase in enzyme release or in glucosamine uptake. Although chemically prepared dimers of IgG were found sufficient to trigger the macrophages, both enzyme release and glucosamine incorporation increased with the size of the IgG aggregates. Similarly, immune complexes in IgG antibody excess (Ag/Ab ratio 1:32) were more efficient than complexes prepared at equivalence or in antigen excess, which suggests that the size of the aggregates is an important parameter of macrophage triggering. The participation of the macrophage Fc receptor for IgG in IgG-dependent macrophage triggering is suggested by similar findings using a first exposure of the cells to rat IgG then the cross-linking the cell-bound immunoglobulin by purified anti-rat IgG or the F(ab')2 fragment of it. Macrophage function in inflammatory reaction might thus be modulated by the size of IgG immune complexes.