Induction of antigen-specific bronchial reactivity to trimellityl-human serum albumin by passive transfer of serum from humans to rhesus monkeys.
A rhesus monkey model was developed to demonstrate the pathogenetic role of IgE to chemical hapten-protein conjugates in causing human occupational asthma from reactive chemicals. Serum from a worker with trimellitic anhydride (TMA) asthma that contained high titers of IgE, IgG, IgM, and IgA to trimellityl-human serum albumin (TM-HSA) was aerosolized into the lungs of two monkeys to afford passive airway sensitization. After the monkeys were challenged with aerosolized TM-HSA, pulmonary functions demonstrated acute airway responses similar to that of Ascaris antigen-induced, IgE-mediated bronchospasm in Ascaris-sensitive monkeys. The monkeys had no airway reactivity when challenged with TM-HSA 1 week after the first positive TM-HSA response elicited with passive sensitization. Passive cutaneous reactivity to TM-HSA was also elicited by the donor serum, but heat-treated donor serum failed to confer cutaneous or bronchial reactivity. These results indicate that airway reactivity in this passive-transfer monkey model of TMA asthma is an antigen-specific response mediated by heat-labile serum factors, presumably IgE to TM-HSA, and does not occur by irritant mechanisms. This experimental model could become a valuable system for evaluating the role of IgE to hapten-protein conjugates in the immunopathogenesis of asthma caused by other reactive chemicals capable of acting as haptens. We postulate that immunologic and clinical features should be consistent with asthma caused by such reactive chemicals and mediated by such mechanisms.
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000947:Antigens, Helminth / Q000276:immunology; D001200:Ascaris / Q000276:immunology; D001769:Blood / Q000276:immunology; D001980:Bronchi / Q000276:immunology*; D001985:Bronchial Provocation Tests; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006358:Hot Temperature; D006801:Humans; D007116:Immunization, Passive; D008253:Macaca mulatta; D010795:Phthalic Acids / Q000276:immunology*; D010796:Phthalic Anhydrides / Q000276:immunology*; D012709:Serum Albumin / Q000276:immunology*
D000906:Antibodies; D000947:Antigens, Helminth; D000939:Epitopes; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; D012709:Serum Albumin; C015559:trimellitic anhydride