Role of the VLA-4 integrin in leucocyte recruitment and bronchial hyperresponsiveness in the guinea-pig.

Guinea-pigs sensitized to ovalbumin develop airway eosinophilia and bronchial hyperresponsiveness to acetylcholine 24 h following ovalbumin challenge. We have used an antibody to the very late antigen-4 (VLA-4) integrin (HP 1/2) to investigate the role of this integrin in the recruitment of leucocytes to the airways and to study the link between eosinophilia and the development of bronchial hyperresponsiveness. In this model, HP 1/2 reduced the number of eosinophils recovered from bronchoalveolar lavage fluid, as well as reducing the activity of the enzyme eosinophil peroxidase in both bronchoalveolar lavage fluid and whole lung extracts. However, HP 1/2 did not reduce bronchial hyperresponsiveness. The results suggest that after antigen challenge, the VLA-4 integrin is involved in the recruitment of leucocytes to the airways at the level of the vascular endothelium, but increased numbers of eosinophils in lavage fluid or in the lung tissue are not an essential correlate of bronchial hyperresponsiveness in this model.