ANTIBODY TO VERY LATE ACTIVATION ANTIGEN-4 PREVENTS ANTIGEN-INDUCED BRONCHIAL HYPERREACTIVITY AND CELLULAR INFILTRATION IN THE GUINEA-PIG AIRWAYS

This report examines the effect of an anti-VLA-4 monoclonal antibody ( mAb) HP1/2 on antigen-induced bronchial hyperreactivity to methacholin e, and on eosinophil and T lymphocyte infiltration in the airways of g uinea pigs sensitized and challenged by aerosolized ovalbumin and used 24 h thereafter. The intravenous administration of 2.5 mg/kg of HP1/2 , but not of its isotype-matched mAb 1E6, 1 h before and 4 h after ant igen inhalation, markedly inhibited the increased bronchopulmonary res ponses to intravenous methacholine, as well as airway eosinophilia in bronchoalveolar lavage (BAL) fluid and in bronchial tissue. HP1/2 also suppressed the antigen-induced infiltration of the bronchial wall by CD4(+) and CD8(+) T lymphocytes, identified by immunohistochemical tec hnique using specific mAbs that recognize antigenic epitopes of guinea pig T cells. Treatment with HP1/2 also resulted in a significant incr ease in the number of blood eosinophils, suggesting that inhibition by anti-VLA-4 mAb of eosinophil recruitment to the alveolar compartment may partially account for their accumulation in the circulation. These findings indicate that eosinophil and lymphocyte adhesion and subsequ ent infiltration into the guinea pig airways that follow antigen chall enge are mediated by VLA-4. Furthermore, concomitant inhibition of ant igen-induced bronchial hyperreactivity and of cellular infiltration by anti-VLA-4 mAb suggests a relationship between airway inflammation an d modifications in the bronchopulmonary function.