Mast cell involvement in the adenosine mediated airway hyper‐reactivity in a murine model of ovalbumin‐induced lung inflammation

1 Airway hyper‐reactivity to inhaled adenosine, mediated via mast cell activation, is a cardinal feature of asthma. Animal models have been developed in several species to mimic this phenomenon, but only in the rat has a mast cell involvement been clearly defined. In this study, a model of ovalbumin‐induced adenosine hyper‐reactivity was developed in BALB/c mice to determine whether mast cells are involved in this phenomenon. 2 Sensitised mice were challenged one, two or three times, on a daily basis, and airway responses to the stable adenosine analogue NECA (5′‐ N ‐ethylcarboxamido adenosine) determined 4 and 24 h after each challenge. Airway hyper‐reactivity was observed in ovalbumin‐challenged mice 4 h after a single challenge and to a minor extent 24 h after a single challenge and 4 h after two challenges. 3 Cromolyn (20 mg ml −1 ), given by aerosol an hour before the NECA provocation, fully inhibited the airway hyper‐reactivity observed 4 h after a single allergen challenge, suggesting a role for mast cells in this response. The airway space cellular inflammation was not affected by cromolyn. 4 As observed in human asthma, an acute treatment with steroid (budesonide 3 mg kg −1 , given an hour before the allergen challenge) inhibited the NECA airway hyper‐reactivity and significantly inhibited the airway space cellular inflammation. 5 These data suggest that the ovalbumin‐challenged BALB/c mice can be considered as a suitable model to study the adenosine‐induced airway hyper‐reactivity phenomenon observed in human asthma.British Journal of Pharmacology (2005) 145 , 845–852. doi: 10.1038/sj.bjp.0706271