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

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. 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. 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. 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. 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.