Receptor-specific mediation by immunoglobulin E of antigen-induced contraction of tracheal and lung parenchymal strips isolated from the guinea pig.

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Abstract

The guinea pig is much like humans in the cells and mediators involved in immediate hypersensitivity reactions. However, the major anaphylactic antibody in this species is IgG1, not IgE. Recently, we have been successful in producing IgE antibody in guinea pigs. The current study examined whether guinea pig IgE antibody could mediate pulmonary smooth muscle contraction. IgE antibody to picryl and oxazolone determinants was induced by immunizing Hartley strain guinea pigs pretreated with cyclophosphamide. Hyperimmune serum from these animals was passed through a heavy chain-specific anti-IgG1 affinity column. The presence of IgE anti-hapten antibody in the filtrate fraction was verified by passive cutaneous anaphylaxis (PCA) testing with a 7-d period of local passive sensitization and by heat lability (56 degrees C X 4 h) of PCA activity. This IgE-rich fraction, and purified IgG1 anti-hapten antibody were transferred to normal guinea pigs. Both fractions sensitized trachea and pulmonary parenchyma for antigen-induced smooth muscle contraction. The IgG1-mediated antigen-induced contractile response was not affected by heat (56 degrees C X 4 h) and was inhibited in a dose-dependent fashion by IgG1 blocking antibody (anti-OA). The IgE-mediated antigen-induced contractile response was significantly decreased by heat and was not affected by the anti-OA blocking antibody even at a concentration of 100 mg/kg. Thus, two antigen-specific factors in guinea pig serum can mediate antigen-induced pulmonary smooth muscle contraction: IgG1 and IgE antibodies. Our data also suggests that these antibodies mediate the contractile response through separate receptors. The finding that guinea pig IgE can mediate pulmonary smooth muscle contraction suggests this species can be a model for IgE-mediated events in the lung.

Authors

F M Graziano, L Gundersen, L A Larson, P Harley, C K Buckner