We have determined that the interaction of IgG-coated erythrocytes (EIgG) and complement-coated erythrocytes (EIgMC) with macrophage Fc and complement receptors, respectively, modulates the secretion of the neutral proteinases, elastase, and plasminogen activator. EIgG binding and ingestion stimulated secretion of elastase and plasminogen activator less than or equal to 6-fold and 20-fold, respectively, over the 3 d following treatment. Stimulation was dependent on the IgG titer bound to each erythrocyte and was detectable at greater than 6.2 X 10(3) molecules IgG/ erythrocyte (total 0.99 nM IgG in the culture). Cytochalasin B did not inhibit stimulation, indicating that the ingestion of ligands was not necessary. Binding of EIgG to the three subclass-specific Fc receptors (IgG2a, IgG2b/IgG1, IgG3) was effective. Stimulation of elastase secretion required continued exposure of ligands to cells for up to 24 h, whereas production of plasminogen activator, which has plasma membrane-bound forms as well as secreted forms, was stimulated by exposure for 2 h. The stimulated production of elastase and plasminogen activator by triggering Fc receptors was seen only when the initial secretion rates were low. Periodate- or thioglycollate-elicited macrophages, which have high rates of proteinase secretion, were not stimulated further. EIgMC, which are bound but not ingested by resident macrophages, stimulated elastase secretion transiently, and the rate of secretion returned to the control level by 24 h. Therefore, the mode of stimulation of neutral proteinase secretion by complement receptor differed from that of Fc receptor; stimulation by complement receptor possibly involves a limited release of enzyme from intracellular stores, rather than stimulating accelerated synthesis of enzyme. Erythrocytes coated with both complement and IgG showed both the transient increase in elastase typical of complement-mediated secretion and the sustained increase typical of Fc receptor-mediated secretion. These results suggest that macrophage Fc and complement receptors regulate secretion of proteinases by receptor-specific mechanisms.

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