A Monoclonal Antibody to 11 Blocks Antigen-induced Airway Responses in Sheep

The integrin 11 (very late antigen-1; CD49a/CD29) is a major adhesion receptor for collagen I, IV, and VI, and its induced expression on activated monocytes and lymphocytes plays a central role in their retention and activation at inflammatory sites in autoimmune pathol- ogies. However, the role of 11 in allergic settings has not been explored. In this study, we show that a single 45-mg dose of aerosol- ized monoclonal antibody AQC2 to the 1 chain of human and sheep very late antigen-1, given 30 minutes before challenge, blocks both the allergen-induced late response and the associated airway hyper- responsiveness, functional indicators of allergen-induced inflamma- tion, in sheep. AQC2 does not affect the early response. Consistent with these effects, AQC2 tended to reduce the cell response associ- ated with local antigen instillation. An isotype-matched control anti- body had no protective effects. Two humanized versions of AQC2, a wild-type IgG1 and an aglycosyl form of the same monoclonal antibody, which has reduced Fc receptor-mediated effector func- tions, are equally effective in blocking the antigen-induced late re- sponse and airway hyperresponsiveness in the sheep model. These data suggest that mononuclear leukocyte adhesion-dependent pa- thologies contribute to allergic lung disease and provide proof-of- concept that antagonists of 1 integrins may be useful in preventing these events.