Late-breaking abstract: A novel model of IgE-mediated passive pulmonary anaphylaxis in rats

Background : Mast cells are central effector cells in asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation is an important intervention point to inhibit bronchoconstriction, airway oedema and inflammation. Aim : To develop a novel model of pulmonary anaphylaxis in rats. Methods : Rats were passively sensitized by i.t. and i.d. (ear) with an anti-DNP IgE antibody. DNP-BSA in Evans blue dye, was applied i.v. 24 hours later. Quantification of mast cell degranulation in the ear and lung was determined by (1) extravasation of Evans blue in bronchial and ear tissue, (2) changes in airway resistance, and (3) release of mediators into the airways. Results : Histamine was transiently present in the airways that coincided with bronchoconstriction, but preceded vascular leakage. The model was pharmacologically validated with the mast cell stabilizer cromoglycate (CG), the H1 receptor antagonist Desloratadine, the β2-adrenergic agonist Formoterol, the corticosteroid Prednisolone and the SYK inhibitor Fostamatinib. CG attenuated both vascular leakage and bronchoconstriction, but with a very short duration of action. Desloratadine effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against pulmonary vascular leakage. Inhaled Formoterol was more effective in the lung than in the ear and oral Fostamatinib was equally efficacious in lung and ear. Prednisolone did not inhibit responses in the ear or lung. Conclusions : This model of passive pulmonary anaphylaxis provides a tissue relevant readout of early mast cell activity and pharmacological benchmarking reflects responses observed in asthmatic patients.