Introduction of B-chain-inactivated ricin into mouse macrophages and rat Kupffer cells via their membrane Fc receptors.
Experiments have been made to test whether the toxic lectin ricin can be bound to and introduced into cells by some other mechanism than via its B chain, the natural binding moiety of the toxin, without its toxic effect being neutralized. Complexes consisting of ricin and antibodies specifically directed against ricin B chain were incubated with mouse peritoneal macrophages and rat Kupffer cells, which are known to possess surface receptors for the Fc portion of the immunoglobulin molecule. After incubation for 26 h, cellular protein synthesis, as measured by incorporation of labeled leucine into acid-insoluble material, was completely inhibited. HeLa cells, which do not possess Fc receptors, were unaffected by the complex. The effect of the complex on protein synthesis of macrophages was prevented by soluble antigen-antibody complexes, but not by the presence of lactose which prevents attachment of the ricin B chain to the cell membrane. The [ricin-antiricin B] complex was attached to red cells, and the resulting complex was incubated with rat Kupffer cells. Cellular protein synthesis ceased after 6 h, and phase contrast microscopy studies showed that the complexes were taken up by the Kupffer cells. The data indicate that ricin, when present in the complex with antiricin B, can be introduced into cells through cell membrane receptors other than the B chain receptor, in this case the Fc receptor, and that the internalized toxin retains a least part of its activity.
D000818:Animals; D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D004705:Endocytosis; D005260:Female; D006367:HeLa Cells; D007141:Immunoglobulin Fc Fragments; D007728:Kupffer Cells / Q000276:immunology; D007785:Lactose / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D010940:Plant Proteins / Q000276:immunology; D014176:Protein Biosynthesis; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D012276:Ricin / Q000276:immunology / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000936:Antigen-Antibody Complex; D007141:Immunoglobulin Fc Fragments; D010940:Plant Proteins; D011955:Receptors, Drug; D012276:Ricin; D007785:Lactose