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 number in the mucosa after antigen challenge and depend on the expression of alpha4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevent 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 site. 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 per cent 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.

Emergence of T-lymphocytes, eosinophils and dendritic cells in the bronchi of actively sensitized guinea pigs after antigenic challenge

Bronchi from guinea pigs actively sensitized to ovalbumin and boosted two weeks later display increased numbers of CD4+ T-lymphocytes and eosinophils. We have further investigated immunopathological changes in sensitized guinea pigs 2 or 24 h after antigenic challenge with ovalbumin. Lungs were resected, frozen and cryostat sections stained with monoclonal antibodies that recognize relevant guinea pig epitopes. Cyanide-resistant peroxidase activity was used to stain eosinophils. No further increase in T-lymphocytes or eosinophils was observed 2 h after challenge. At 24 h, a marked increase in EPO+ eosinophils was found, and this was accompanied by severe mucosal damage characterized by epithelial shedding and ulceration. The numbers of T-lymphocytes remained stable but a novel population of cells with the appearance of dendritic cells was seen in the bronchial wall. They were negative for macrophage markers but were strongly Class II positive. These findings suggest that antigenic challenge results in further recruitment of eosinophils, their activation and release of toxic substances to the epithelium. Furthermore, other cell types, possibly dendritic cells, are attracted to the bronchi and could play a role in maintaining allergic inflammation via antigen presentation.