Inhibition of macrophage tumoricidal activity by immune complexes and altered erythrocytes.
Engagement of the macrophage membrane by biologic particles including insoluble immune complexes inhibited the development of lymphokine-mediated nonspecific tumoricidal activity by murine macrophages. The degree of inhibition was dependent on the dose of particles and the lymphokine concentration. Inhibition was not due to macrophage cell death or to diminution of cell adherence after ingestion of the immune complexes. Soluble immune complexes were not inhibitory, although approximately 10% of the complexes became cell-associated. Monomeric or heat-aggregated IgG was also not inhibitory. IgG-opsonized erythrocytes (EA) were inhibitory and inhibition was dependent on the degree of opsonization. In contrast, nonopsonized erythrocytes (E), which did not bind to macrophages, were not inhibitory. Phagocytosis of glutaraldehyde-treated E or E carrying IgM antibody and complement (EAC) also led to a reduction of tumorilytic activity. Insoluble immune complexes were inhibitory when added either before or after lymphokine. Phagocytosis was neither sufficient nor necessary to cause inhibition because 1) ingestion of polystyrene latex beads did not diminish tumoricidal activity, and 2) macrophages plated on IgG-coated surfaces were inhibited with respect to the tumoricidal function. Inhibition was not affected when indomethacin (10(-6) M) was included in the assay, which indicated that prostaglandins were not involved in the process. Thus, macrophage tumoricidal responsiveness may be compromised by interaction of biologic substances with macrophage plasma membranes. This process may thereby inactivate an important host defense mechanism against neoplastic cells.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004705:Endocytosis; D004912:Erythrocytes / Q000502:physiology*; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000378:metabolism; D008262:Macrophage Activation; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D009895:Opsonin Proteins / Q000502:physiology; D010587:Phagocytosis; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D011453:Prostaglandins