A MONOCLONAL-ANTIBODY AGAINST VERY LATE ACTIVATION ANTIGEN-4 INHIBITSEOSINOPHIL ACCUMULATION AND LATE ASTHMATIC RESPONSE IN A GUINEA-PIG MODEL OF ASTHMA

Preferential eosinophil accumulation is a characteristic of airway inf lammation in asthma. Although little is known about its mechanism, rec ent in vitro observations suggest that the very late activation antige n-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclon al antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumi n. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, wh en guinea pigs were pretreated intravenously at 2 h before antigen cha llenge with a rat anti-mouse VLA-4 mAb, PS2/3, cross-reacting with gui nea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocy te infiltration in the tracheal wall was significantly inhibited as we ll as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.