ROLE OF THE VLA-4 INTEGRIN IN LEUKOCYTE RECRUITMENT AND BRONCHIAL HYPERRESPONSIVENESS IN THE GUINEA-PIG

Guinea-pigs sensitized to ovalbumin develop airway eosinophilia and br onchial 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 rec ruitment of leucocytes to the airways and to study the link between eo sinophilia and the development of bronchial hyperresponsiveness. In th is model, HP 1/2 reduced the number of eosinophils recovered from bron choalveolar lavage fluid, as well as reducing the activity of the enzy me eosinophil peroxidase in both bronchoalveolar lavage fluid and whol e lung extracts. However, HP 1/2 did not reduce bronchial hyperrespons iveness. The results suggest that after antigen challenge, the VLA-4 i ntegrin is involved in the recruitment of leucocytes to the airways at the level of the vascular endothelium, but increased numbers of eosin ophils in lavage fluid or in the lung tissue are not an essential corr elate of bronchial hyperresponsiveness in this model.