IgG vs IgE: Mediators of antigen-induced guinea pig tracheal contraction

Abstract

Guinea pig IgG and IgE were employed in these studies to determine whether different mediators were responsible for IgG- and IgE-mediated contraction of guinea pig trachea. Isolated tracheal strips were passively sensitized using IgG- or IgE-type antibody to ovalbumin which had been separated using Protein A Sepharose. The antigen-induced contraction of tracheae sensitized with either IgG or IgE was delayed by diphenhydramine (10−5 M) and significantly enhanced by aspirin (1.1 × 10−4 M). The leukotriene antagonist FPL 55712 (1.9 × 10−5 M) decreased the duration of the IgG-mediated contraction but not that of the IgE-mediated contraction. Diphenhydramine in combination with FPL 55712 caused a greater inhibition of the IgG-mediated tracheal contraction than either antagonist alone. In contrast, the IgE-mediated response was inhibited to the same extent by a combination of FPL 55712 and diphenhydramine as with diphenhydramine alone. The lipoxygenase inhibitor nordihydroguaiaretic acid in combination with diphenhydramine inhibited the antigen-induced contraction to a greater extent than diphenhydramine alone in the IgG, but not in the IgE-sensitized trachea. Leukotriene release from trachea was assessed by contraction of the longitudinal muscle of an unsensitized guinea pig ileum mounted in the same tissue bath. On ovalbumin challenge, leukotriene release was detected from IgG-sensitized trachea but only minimally from IgE-sensitized trachea. Histamine release was detectable on antigen challenge of IgG- and IgE-sensitized trachea. Heating IgG (56°C for 4 h) did not alter its ability to mediate histamine or leukotriene release. However, heating IgE prior to sensitizing the trachea resulted in a significant reduction in histamine release. These data suggest that leukotrienes play an important role in IgG- but not IgE-mediated tracheal contraction and that an unidentified mediator other than leukotrienes is responsible for the IgE-mediated tracheal contraction.