[Role of adhesion molecules (VLA-4) in the asthmatic response to allergens]

We evaluated the role of very late antigen-4 (VLA-4) in asthmatic responses. Brown-Norway rats were sensitized with ovalbumin and then challenged with ovalbumin. Respiratory impedance, and the influx of eosinophils and of VLA-4-positive cells were measured. Eosinophils were stained with Giemsa's solution and VLA-4-positive cells were detected by an immunocytochemical method with a monoclonal antibody against rat VLA-4 (MR alpha 4-1). The numbers of eosinophils and of VLA-4-positive cells in sections of lung tissue from the rats were counted. The effect of MR alpha 4-1 and of a new anti-allergic drug, TYB-2285, on late asthmatic responses was also studied. Respiratory impedance had increased in all the rats by 6-7 hours after the challenge, which indicated that these animals had a late asthmatic response. These rats had more eosinophils and more VLA-4-positive cells than did sensitized animals that were not challenged. The rats given MR alpha 4-1 had significantly smaller increases in respiratory impedance and less eosinophil influx than did those given only phosphate-buffered saline. The rats given TYB-2285 had significantly smaller increases in impedance and less influx of eosinophils and of VLA-4-positive cells. These results show that infiltration of eosinophils and of VLA-4-positive cells corresponds closely with the late asthmatic response, and they suggest that the VLA-4/VCAM-1 pathway plays an important role in this response. These data also suggest that the infiltration of VLA-4-positive cells can be used to evaluate the effect of anti-allergic drugs on the late asthmatic response.