Pulmonary Antigen Challenge in Rats Passively Sensitized with a Monoclonal IgE Antibody Induces Immediate But Not Late Changes in Airway Mechanics

Pulmonary antigen challenge in sensitized individuals results in isolated immediate, isolated late, or dual reactions consisting of both an immediate and late change in airway function. The immediate response appears to be dependent on the presence of IgE antibody and mast cell mediator release. Although the late phase of dual responses is considered to be related to or a continuum of the immediate hypersensitivity response, its precise pathogenesis remains to be determined. To increase both the sensitivity and specificity of analyzing the pathogenesis of IgE-dependent pulmonary responses, we have used a Sprague-Dawley rat model system in which rats are passively sensitized with a murine monoclonal IgE anti-dinitrophenol (DNP) antibody prior to challenge with DNP-bovine serum albumin (DNP-BSA). Pathogen-free rats were injected with IgE or saline in a randomized blinded protocol, and in 24 to 48 h were anesthetized with urethane (1.2 g/kg intraperitoneally) and instrumented to measure lung resistance (Rl) and dynamic compliance (Cdyn). Rats were then challenged with aerosolized DNP-BSA (10 mg/ml), and Rl and Cdyn monitored through 7 h after challenge. Both Rl (0.30 ± 0.10 versus 0.13 ± 0.02 cm H2O/ml·sec−1) and Cdyn (0.41 ± 0.10 versus 0.25 ± 0.08 ml/cm H2O) were significantly different (p < 0.05) in sensitized rats compared to control rats immediately after challenge. No late changes were observed in either the treated or control animals. Similar lung mechanics were measured in animals that were challenged with DNP-BSA aerosol while awake and then anesthetized 3.5 or 8 h later. These latter results indicate that urethane anesthesia did not suppress the development of late changes in lung mechanics after challenge. We conclude that, after passive sensitization with a murine monoclonal IgE antibody, pulmonary antigen challenge in rats results in isolated immediate responses. Thus, the presence of IgE antibody alone may be sufficient to induce the immediate response, but additional immunologic or physiologic factors may be necessary to produce late changes in lung mechanics after antigen challenge in this species.