Cytophilic binding of IgE to the macrophage. II. Immunologic release of lysosomal enzyme from macrophages by IgE and anti-IgE in the rat: a new mechanism of macrophage activation.

Rat peritoneal macrophages release lysosome granule-associated β-glucuronidase, but not cytoplasmic leucine aminopeptidase, after successive incubation with purified IgE protein and ?-specific anti-IgE antibody or anti-IgE F(ab′)₂ fragments. The selective release of β-glucuronidase was shown to proceed by a first step of binding of the purified IgE to the cell surface, followed by IgE-anti-IgE reaction on the macrophage, whereas the possibility of cell activation by IgE-anti-IgE complexes in the bulk phase was ruled out. Heating rat IgE destroyed its ability to mediate lysosomal enzyme release. The characteristics of macrophage activation, insofar as the binding of IgE is concerned, were in agreement with those reported for the fixation of IgE to the mononuclear phagocyte, optimal binding of IgE being achieved with 20 min incubation. Preincubation of rat macrophages with rat IgG, either aggregated or not aggregated, did not inhibit the selective release of β-glucuronidase by the successive addition of IgE and anti-IgE antibody. Simultaneous incubation of macrophage monolayers with rat IgE and aggregated rat IgG did not reduce the subsequent activation by addition of anti-IgE. These studies indicated that rat macrophages can bind rat IgE through a specific receptor, with no interference of the classical Fc (γ) receptor, and are triggered to release lysosomal enzymes upon conformational changes of the IgE molecule by anti-IgE antibody. Antibody-dependent macrophage cytotoxicity in rat schistosomiasis is mediated by IgE antibody to the parasite, which may therefore function by activating the macrophage to an efficient effector cell.