THE IMPORTANCE OF LEUKOTRIENES IN AIRWAY INFLAMMATION IN A MOUSE MODEL OF ASTHMA

Inhalation of antigen in immunized mice induces an infiltration of eos inophils into the airways and increased bronchial hyperreactivity as a re observed in human asthma. We employed a model of late-phase allergi c pulmonary inflammation in mice to address the role of leukotrienes ( LT) in mediating airway eosinophilia and hyperreactivity to methacholi ne. Allergen intranasal challenge in OVA-sensitized mice induced LTB(4 ) and LTC(4) release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and bronchoa lveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5-lipoxygenas e and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus re lease and infiltration by eosinophils indicating a key role for leukot rienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine mod el.