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.
Wyss
Daniel
D
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham RH12 5AB, UK.
Bonneau
Olivier
O
Trifilieff
Alexandre
A
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007114:Immunization; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D019819:Budesonide; D010047:Ovalbumin; D004205:Cromolyn Sodium