Suppression of IgE antibody production in sensitized mice and rats by tolerogenic conjugates of synthetic hydrophilic polymers with antigen or hapten: effect on antigen-induced histamine release from peritoneal mast cells.
IgE antibodies were produced in mice and rats by immunization with ragweed pollen extract (RAG) or dinitrophenylated ovalbumin (DNP3-OA). Treatment of these animals with tolerogenic conjugates of (i) the antigen (RAG or OA) with monomethoxypolyethylene glycol (mPEG), or (ii) DNP with polyvinyl alcohol (DNP-PVA) resulted, within 7-14 days, in a fall in circulating IgE antibodies and in mast cell sensitivity, as assessed by the radioallergosorbent test (RAST) and in the in vitro antigen-induced histamine release (HR) test, respectively. The reduction in responsiveness was more marked in mice than rats; 10 days after a booster immunization, the IgE antibody titres in the RAG-mPEG-treated group of mice were approximately 10-fold lower than in the saline-treated group, with a 100-fold difference in cell sensitivity. DNP-PVA treatment of mice produced a more than 10-fold reduction in IgE anti-DNP titres with a substantial reduction in histamine release.
D000818:Animals; D004136:Dinitrobenzenes / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D006636:Histamine Release; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010047:Ovalbumin / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D011142:Polyvinyl Alcohol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water / Q000378:metabolism
D004136:Dinitrobenzenes; D006241:Haptens; D007166:Immunosuppressive Agents; D011108:Polymers; D014867:Water; D007073:Immunoglobulin E; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; C028210:monomethoxypolyethylene glycol; D010047:Ovalbumin