Role of eosinophilic airway inflammation in models of asthma.
Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in numbers in the mucosa after antigen challenge and depend on the expression of alpha 4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha 4 integrin expression with specific antibody prevents not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR) to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional state. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100% the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.
Lapa e Silva
J R
JR
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM no. 285, Paris, France.
Ruffié
C
C
Lefort
J
J
Pretolani
M
M
Vargaftig
B B
BB
D000818:Animals; D015703:Antigens, CD; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000502:physiology*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000276:immunology; D039441:Integrin alpha4
D015703:Antigens, CD; D039441:Integrin alpha4