LEUKOTRIENES IN BILE DURING THE EARLY AND THE LATE AIRWAY RESPONSES AFTER ALLERGEN CHALLENGE OF SENSITIZED RATS

The Brown Norway rat produces high levels of IgE in response to active immunization and develops both early and late airway constrictor responses after subsequent allergen challenge. We have used this model of allergic asthma to investigate the temporal relationship between the in vivo synthesis of peptidoleukotrienes (peptido-LTs) and the late response. Brown Norway rats that had been sensitized by injection of ovalbumin 2 to 3 wk prior to the commencement of the experiment were subjected to bile duct cannulation and tracheal intubation. The rats were challenged 2 h later by intratracheal instillation of ovalbumin. Lung resistance was measured before and at frequent intervals after antigen challenge. Biliary peptido-LTs (LTC4, LTD4, LTE4, and N-acetyl-LTE4) were measured by a combination of high pressure liquid chromatography and radioimmunoassay in bile samples collected for a period of 1 h before instillation of ovalbumin, and between zero and 1 h, 1 and 4 h, 4 and 6 h, and 6 and 8 h, subsequently. All of the 10 rats subjected to antigen challenge developed early responses. Of these, six also developed late responses, whereas two died about 1 h after challenge. The levels of peptido-LTs excreted in bile between 4 and 8 h after antigen challenge (corresponding in time to the late responses) were about four times higher in the ovalbumin-instilled rats that developed late responses (n = 6) than in the ovalbumin-sensitized control rats that had been subjected to instillation of saline (n = 6; p < 0.02). The results strongly implicate peptido-LTs as important mediators of the late airway response after antigen challenge of the Brown Norway rat, a model of allergic asthma.